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Treatment Algorithm for Chronic Idiopathic Constipation and Constipation-Predominant Irritable Bowel Syndrome Derived from a Canadian National Survey and Needs Assessment on Choices of Therapeutic Agents

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Background . Chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) are common functional lower gastrointestinal disorders that impair patients’ quality of life. In a national survey, we aimed to evaluate (1) Canadian physician practice patterns in the utilization of therapeutic agents listed in the new ACG and AGA guidelines; (2) physicians satisfaction with these agents for their CIC and IBS-C patients; and (3) the usefulness of these new guidelines in their clinical practice. Methods . A 9-item questionnaire was sent to 350 Canadian specialists to evaluate their clinical practice for the management of CIC and IBS-C. Results . The response rate to the survey was 16% ( n=55 ). Almost all (96%) respondents followed a standard, stepwise approach for management while they believed that only 24% of referring physicians followed the same approach. Respondents found guanylyl cyclase C (GCC) agonist most satisfying when treating their patients. Among the 69% of respondents who were aware of published guidelines, only 50% found them helpful in prioritizing treatment choices and 69% of respondents indicated that a treatment algorithm, applicable to Canadian practice, would be valuable. Conclusion . Based on this needs assessment, a treatment algorithm was developed to provide clinical guidance in the management of IBS-C and CIC in Canada.
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Research Article
Treatment Algorithm for Chronic Idiopathic
Constipation and Constipation-Predominant Irritable Bowel
Syndrome Derived from a Canadian National Survey and
Needs Assessment on Choices of Therapeutic Agents
Yvonne Tse,1David Armstrong,2Christopher N. Andrews,3Alain Bitton,4Brian Bressler,5
John Marshall,2and Louis W. C. Liu1
1Un iversit y o f To r onto , Toron t o, ON, C a n a d a
2McMaster University, Hamilton, ON, Canada
3University of Calgary, Calgary, AB, Canada
4McGill University, Montreal, QC, Canada
5University of British Columbia, Vancouver, BC, Canada
Correspondence should be addressed to Louis W. C. Liu; louis.liu@uhn.ca
Received  July ; Revised  November ; Accepted  December ; Published  February 
Academic Editor: Dina Kao
Copyright ©  Yvonne Tse et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background. Chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) are common
functional lower gastrointestinal disorders that impair patients’ quality of life. In a national survey, we aimed to evaluate ()
Canadian physician practice patterns in the utilization of therapeutic agents listed in the new ACG and AGA guidelines; ()
physicians satisfaction with these agents for their CIC and IBS-C patients; and () the usefulness of these new guidelines in
their clinical practice. Methods. A -item questionnaire was sent to  Canadian specialists to evaluate their clinical practice
for the management of CIC and IBS-C. Results.eresponseratetothesurveywas%(𝑛=55). Almost all (%) respondents
followed a standard, stepwise approach for management while they believed that only % of referring physicians followed the
same approach. Respondents found guanylyl cyclase C (GCC) agonist most satisfying when treating their patients. Among the
% of respondents who were aware of published guidelines, only % found them helpful in prioritizing treatment choices and
% of respondents indicated that a treatment algorithm, applicable to Canadian practice, would be valuable. Conclusion.Basedon
this needs assessment, a treatment algorithm was developed to provide clinical guidance in the management of IBS-C and CIC in
Canada.
1. Introduction
Chronic idiopathic constipation (CIC) and irritable bowel
syndrome with predominant constipation (IBS-C) are com-
mon gastrointestinal disorders in North America, with CIC
aecting –% [] of the general population and IBS-C
aecting .% []. Canada is amongst one of the countries
that carry a high rate of IBS in the world, with a prevalence
estimated to be  in  in the population and an incidence of
, new cases per year [, ]. IBS-C is more common
in females and younger adults of less than  years of age,
whereas CIC aects females and older adults more commonly
[]. CIC and IBS-C impair patients quality of life (QoL), sim-
ilar to those suered from asthma and rheumatoid arthritis,
and negatively impact socioeconomics of the society [, ].
Although the Rome III diagnostic criteria dene CIC and
IBS-C as separate entities, with IBS-C being distinguished by
the presence of abdominal pain and discomfort, these criteria
cannot distinguish reliably between CIC and IBS-C. Many
patients have features of both disorders and their diagnosis
may change over time [, ]. In , America College of
Gastroenterology (ACG) published a systematic review on
Hindawi
Canadian Journal of Gastroenterology and Hepatology
Volume 2017, Article ID 8612189, 11 pages
https://doi.org/10.1155/2017/8612189
Canadian Journal of Gastroenterology and Hepatology
the ecacy of available therapy in IBS and CIC []. Earlier
in , American Gastroenterological Association (AGA)
published a medical position statement on constipation [],
followed by an AGA guideline on pharmacological manage-
ment of IBS in  []. However, all these guidelines did
not provide direction in terms of the priority of when the
therapeutic agents are recommended to be used to optimize
management in patients suering from CIC and IBS-C.
Usinganationalsurvey,weaimedtoevaluateCanadian
specialists’ practice patterns in the utilization and satisfac-
tion of various therapeutic agents for their CIC and IBS-
C patients. e survey also addressed if the respondents
found the new ACG guidelines useful for them to prioritize
which agents to use in their clinical practice. Informed by the
result of this needs assessment survey, a treatment algorithm
was developed for the management of CIC and IBS-C. is
treatment algorithm aligned with the recently published
literature (ACG and AGA guidelines), while also considering
the limitations of these American guidelines in the Canadian
practice.
2. Methods
A questionnaire was sent to  Canadian physicians. Data
were collected over a -month period in early  (CARE,
Toronto, ON) to evaluate respondents’ area of practice and
their constipation management patterns in patients with CIC
and IBS-C.
2.1. Questionnaire. e questionnaire (the Appendix) evalu-
ated physicians’ perceptions and practices with respect to the
management options available in Canada for the treatment
of constipation in patients with CIC and IBS-C. Treatment
options were divided into stool soeners, bre supplements,
stimulant laxatives, osmotic laxatives, prokinetic agents, GCC
agonists, and “other.” Respondents were asked to rank the
order in which they would use these treatment options for
patients with inadequate bre intake, slow-transit consti-
pation, functional outlet constipation, and IBS-C and their
satisfaction with the outcomes of these treatment agents for
their patients with CIC or IBS-C. Satisfaction with treatment
response was recorded on a -point scale from  (very
unsatised),  (dissatised),  (neutral/not sure),  (satised),
to  (very satised). Additional questions regarding strategies
used by referring physicians, awareness of the most recent
ACG guidelines, and questions relating to other practice
characteristicswerealsoincluded.
2.2. Analysis of the Practice Survey. In order to statistically
determine which treatment options were considered most
satisfactory for CIC and IBS-C (the Appendix: Question
(6)(A)and(B)),thequestionswerescaledbasedontheir
rating (number of responses for a particular rating divided
bythetotalnumberofresponses)andthengroupedbased
on whether respondents thought they were not satised (the
Appendix: Question (6) ratings  and ) or satised (the
Appendix: Question (6) ratings  and ). ese 𝑡values were
then calculated to determine the clinical signicance of each.
T : Respondent demographics.
Characteristics Number (%)
Province:
(i) East Coast  (%)
(ii) Quebec  (%)
(iii) Ontario  (%)
(iv) Western Provinces (MB, AB, BC)  (%)
Specialty:
(i) Gastroenterology  (%)
(ii) Not specied/other  (%)
(iii) General surgery  (%)
Practice setting:
(i) Academic  (%)
(ii) Community  (%)
Nonclinical roles:
(i) Education  (%)
(ii) Research  (%)
(iii) Administrative  (%)
Patients seen monthly with chronic constipation
(i) <  (%)
(ii) –  (%)
(iii) –  (%)
(iv) –  (%)
(v) –  (%)
(vi) >  (%)
Majority of respondents were from Ontario and practiced in gastroenterol-
ogy. More than half of the respondents saw at least  patients with chronic
constipation on a monthly basis. Respondents could select more than one
response.
3. Results
3.1. Practice Preferences and Satisfaction of erapeutic Agents.
Completedquestionnaireswerereturnedbyof(%)
physicians although eorts had been made to collect response
via both hardcopy survey and online survey tool with
reminders to encourage participants to respond. Table 
showed the demographic distribution of the respondents.
Almost all (%) respondents reported that they followed
a standard, graduated, or stepwise approach for managing
constipation; however, only % of respondents reported that
referring physicians used a graduated or stepwise approach
in managing patients with constipation. Most respondents
reported that patients (%) and referring physicians (%)
were reluctant to move from over-the-counter (OTC) thera-
pies to prescription medications.
Among the six therapeutic options to manage consti-
pation, the respondents selected osmotic laxatives and bre
supplements/bulking agents as the rst-line (ranked  or  of
question (4) in this survey) treatment of both CIC and IBS-
C (Figure ). Stool soeners were shown to be statistically
the least satisfying treatment option for patients with CIC
(Figure (a), 𝑝 = 0.0002) when analyzing the responses from
those who rated each treatment option as “” (question (6)
of the survey). When ratings of “” and “” (question (6)
Canadian Journal of Gastroenterology and Hepatology
Other
Prokinetic (5-HT4 agonist)
Osmotic laxatives
Stool soeners
Stimulant laxatives
5 1015202530350
(%)
Prosecretory agent
(GCC agonist)
Fibre supplement/bulking
agent
Inadequate bre intake (n=54)
CIC, slow transit (n=54)
CIC, functional outlet obstruction (n=54)
IBS (n=54)
F : Types of treatment patients would ideally receive based
on the type of chronic constipation (the Appendix: Question (4)).
Osmotic laxatives were ranked as rst-line treatment for both CIC
and IBS-C, followed by bre supplements/bulking agents being
second-line treatment for CIC and GCC agonist being second-line
treatment for IBS-C. (CIC:chronic idiopathic constipation; IBS-C:
constipation-predominant irritable bowel syndrome; GCC:guanylyl
cyclase C).
of the survey) were grouped for analysis, stimulant laxatives
werealsofoundtobeanunsatisfyingtreatmentoptionfor
CIC (𝑝 = 0.0002). On the other hand, GCC agonist (𝑝<
0.0001), osmotic laxatives (𝑝 < 0.0001), -HT agonist
(𝑝 = 0.0003), and bre supplements/bulking agents (𝑝=
0.0069) were considered to be satisfying treatments for CIC.
For patients with IBS-C, respondents identied both stool
soeners and stimulant laxatives as signicantly unsatisfying
treatment options (Figure (b), 𝑝 < 0.0001 and 𝑝 = 0.038,
resp.).SimilartothemanagementofCIC,GCCagonist(𝑝<
0.0001), osmotic laxatives (𝑝 < 0.0001), -HT agonist (𝑝=
0.003), and bre supplements/bulking agents (𝑝 = 0.004)
were considered to be satisfying treatments for IBS-C, with
GCC agonist being the most satisfying treatment option (𝑝=
0.03 when ratings of “” were analyzed).
Abdominal pain/bloating were ranked as being the most
burdensome symptoms that aect QoL in patients of CIC
and IBS-C (% and %, Figure ). Our survey indicated
that the respondents reported that their patients least likely
complained of abdominal pain/bloating while using GCC
agonist, suggesting that this agent may be the most eec-
tive to alleviate patients with constipation and abdominal
pain/bloating and least likely to cause these symptoms as side
eects (Figure ).
3.2.AwarenessandPerceptionoftheUsefulnessofACGGuide-
lines. Despite the majority of respondents (%) being aware
of the recent ACG guideline for managing CIC and IBS-C,
only half of the respondents (%, somewhat helpful, %,
very helpful) found the guideline helpful to prioritize the use
of available treatment options. Hence, most of them (%)
expressed great interest in having a treatment algorithm that
wouldbeapplicabletoCanadianpractice.
4. Discussion
Although eorts were made to increase response rate by
using hardcopy survey and online survey tool with reminders
being sent to encourage participation, the response rate
was only % (𝑛=55), which can be a limitation of
generalizability of this study. is may reect the lack of
interest and/or knowledge in this eld of gastroenterology
although this aspect is beyond the scope of this survey.
Nevertheless, we believe that the results of this survey still
provide useful information on gastroenterologists’ practice
in the management of IBS-C and CIC in Canada since we
speculatethatthosewhorespondedtothissurveywerelikely
to be more familiar with the conditions.
eresultsofthissurveyindicatethatmanyspecialists
believe that referring physicians might not follow a similar
stepwise approach to the management of constipation that
many specialists use. is may cause unsatisfactory treatment
outcomes in some patients, resulting in unnecessary referrals.
In addition, results suggest there is the perception that
both patients and/or referring physicians may be reluctant
to move from OTC therapies to prescription agents such
as prucalopride or linaclotide, when the former failed to
provide symptomatic relief. is could be due to a number
of factors, including ease of access and limited reimburse-
ment for prescription medications, prescriber experience and
knowledge of newer treatment options, perceived severity of
taking prescription medications, and dierence in treatment
schedule of OTC versus prescription medications. Responses
collected from this survey suggest that there is a need to
provide education not only to specialists but also to referring
physicians and patients.
Although the Rome diagnostic criteria distinguish IBS-C
from CIC, in clinical practice, these conditions are a spectrum
of illnesses with overlapping symptoms and interchangeable
diagnosis over time in the same patient [, ]. is clinical
observation is consistent with our survey illustrating that
abdominal pain/bloating being most frequently reported
by the respondents to be the most burdensome symptoms
that aect their patients’ QoL in both CIC and IBS-C
(Figure ). e respondents also reported that when GCC
agonist was used to treat their patients with constipation,
their patients least likely complained of abdominal pain and
bloating (Figure ). We believe that this is the underlying
reason the respondents nd using GCC agonist the most
satisfying in treating their patients with CIC and IBS-C
(Figure ). is survey’s outcome was supported by clinical
trial observations that GCC agonist, linaclotide, improves
both bowel movement frequency and abdominal pain [–
].
Canadian Journal of Gastroenterology and Hepatology
Satised
Neutral
Not satised
10 20 30 40 50 60 70 80 90 1000
(%)
Stimulant laxatives
(n=54)
Stool soeners
(n=54)
Osmotic laxatives
(n=54)
Prokinetic
(5-HT4agonist) (n=49)
Fibre supplement/
bulking agent (n=54)
Prosecretory agent
(GCC agonist) (n=50)
(a)
Satised
Neutral
Not satised
10 20 30 40 50 60 70 80 90 1000
(%)
Stimulant laxatives
(n=53)
Stool soeners
(n=52)
Osmotic laxatives
(n=51)
Prokinetic
(5-HT4agonist) (n=48)
Fibre supplement/
bulking agent (n=51)
Prosecretory agent
(GCC agonist) (n=47)
(b)
F : (a) Respondents’ satisfaction with treatment options for managing patients with CIC. Stool soeners and stimulant laxatives
(𝑝 = 0.0002) were found to be unsatisfying treatments for CIC compared to other options. On the other hand, GCC agonist (𝑝 < 0.0001),
osmotic laxatives (𝑝 < 0.0001), -HT agonist (𝑝 = 0.0003), and bre supplements/bulking agents (𝑝 = 0.0069)wereconsideredtobe
satisfying treatments for CIC among the treatment options being surveyed. (CIC:chronic idiopathic constipation; GCC:guanylyl cyclase C.)
(b) Respondents’ satisfaction with treatment options for managing patients with IBS-C. Both stool soeners (𝑝 < 0.0001) and stimulant
laxatives (𝑝 = 0.038) were unsatisfying treatments for IBS-C compared to other options, whereas GCC agonist (𝑝 < 0.0001), osmotic laxatives
(𝑝 < 0.0001), -HT agonist (𝑝 = 0.003), and bre supplements/bulking agents (𝑝 = 0.004) were considered to be satisfying treatments for
IBS-C among the treatment options being surveyed. (IBS-C:constipation-predominant irritable bowel syndrome; GCC:guanylyl cyclase C).
Abdominal pain/bloating
Straining during bowel movements
Sensation of incomplete evacuation
Sensation of anorectal obstruction/blockage
Infrequent stools
5 1015202530350
(%)
CIC (n=54)
IBS-C (n=54)
F : Respondents’ perceptions of symptoms that most aect patients’ quality of life based on the type of constipation. Abdominal
pain/bloating was ranked as being the most burdensome symptom in both CIC (%) and IBS-C (%). (CIC:chronic idiopathic constipation;
IBS-C:constipation-predominant irritable bowel syndrome).
Due to the overall negative impact of CIC and IBS-C
on the patients’ QoL and the health care system, practice
guidelines had been developed. While the recent ACG and
AGA guidelines for CIC and IBS-C management are avail-
able, there are limitations of applying these guidelines directly
in Canadian clinical practice; for example, availability and
accessibility of drugs are dierent between the United States
and Canada. In addition, physician adherence to guidelines is
another limitation of translating these guidelines in clinical
practice. Literature suggests that physician adherence to
Canadian Journal of Gastroenterology and Hepatology
Abdominal pain/bloating
Stimulant laxatives (n=40)
Stool soeners (n=42)
Osmotic laxatives (n=40)
Prokinetic (5-HT4agonist) (n=38)
Fibre supplement/bulking agent (n=49)
Prosecretory agent (GCC agonist) (n=31)
20 40 60 80 1000
(%)
F : Respondents’ perceptions of symptoms that patients most oen complain about while being on various therapy options. For
abdominal pain/bloating, which was being identied as the symptom that most aects patients’ quality of life in both CIC and IBS-C,
patients who were prescribed GCC agonist appeared to be least likely to report abdominal pain/bloating, suggesting that this agent may be the
most eective to alleviate patients with constipation and abdominal pain/bloating. (CIC:chronic idiopathic constipation; IBS-C:constipation-
predominant irritable bowel syndrome; GCC:guanylyl cyclase C).
guidelines is oen quite inadequate [–]. Adherence can
be restricted by several factors, including the length and
complexity of guideline content, the presence of multiple
guidelines (in dierent versions or from dierent groups),
and limited access to the guidelines in a clinical practice
setting [].
Another practical limitation of guidelines, such as the
ACG[]andtheAGA[,]guidelines,isthattheydo
not prioritize the use of recommended agents to achieve
optimal patient outcomes since head-to-head evaluation of
treatment eects of various agents is not usually available.
Hence, it will rely on real-world treating physician experience
to choose which agent to use when various agents receive
strong recommendation. e feedback gathered from the
needs assessment survey clearly indicates that a Canadian-
centered and evidence- and experience-based algorithm that
guides physicians to select the appropriate treatment options
is needed. Based on the responses from this survey, available
evidences, and experience of the authors, we develop an algo-
rithmtohelpphysicianstomanagepatientswithconstipation
(Figure ).
4.1. Development of the Treatment Algorithm
4.1.1. History and Physical Examination. Athoroughhis-
tory and physical examination including digital anorectal
examination (DARE) are important in identifying secondary
causes such as medication-induced constipation (e.g., opi-
oids, calcium-channel blockers, and anticholinergics) and
other underlying medical comorbidities (e.g., diabetes, con-
nectivetissuediseases,andneurologicaldiseases).Ifalarming
features (such as new onset of symptoms aer  years of
age, rectal bleeding, nocturnal symptoms, signicant weight
loss, fever, and anemia) or abnormal physical examination are
identied, the patient should be referred to a specialist for
further assessment to rule out more ominous etiology, such
as malignancy.
e purpose of performing a careful DARE is to identify
patients who may have dyssynergic defecation (DD) as an
etiology of their constipation because management may
involve further investigation such as anorectal manometry
(ARM) or defecography. However, a careful DARE was
found to be accurate with a positive predictive value of
over % compared to ARM in two independent population
cohorts presented with constipation [, ]. When DD is
identied by DARE in patients presented with constipation,
a referral to pelvic health physiotherapists for biofeedback is
recommended to optimize treatment outcomes in addition to
a regular bowel regimen [].
A thorough history and physical examination not only
allow the physicians to assess alarming features or secondary
causes but also allow the physician to establish a therapeutic
relationshipwiththepatient.iswillprovideanopportunity
for the physician to address the patient’s concerns and to
educate the patient about what is being considered to be
normal bowel movements, including the natural variation of
bowel functions and the range of normal stool frequency, as
well as set realistic treatment goals for each individual patient.
Dietary and lifestyle modications (i.e., optimizing dietary
bre and uid intake and encouraging regular physical
activity) should rst be considered as initial management.
Because of the lack of harmful eect of lifestyle and dietary
modication, it is widely accepted and recommended by
experts as rst-line therapy; despite the lack of strong evi-
dence that these measures improve constipation, they have
Canadian Journal of Gastroenterology and Hepatology
e.g., milk of magnesia, lactulose, or PEG
supplements
Trial at a reasonable dose of 4–8 weeks prior
to reassessment of maintenance or
escalation to step-up therapies
Additional agents: Additional therapy:
Pharmacological
e.g., TCA, SSRI, and
SNRL antispasmodic
Nonpharmacological
e.g., meditation,
relaxation, and hypnosis
Fibre supplements Osmotic laxatives Prosecretory agents
e.g., linaclotide
Specialist assessment for
consideration of anorectal
manometry, defecography, and
biofeedback therapy
Eight- to twelve-week trial prior to reassessment
for maintenance or consideration of referral for
specialist assessment
Prosecretory or prokinetic
agents
Unsatisfactory response or intolerant to side eects
Specialist assessment recommended (refer)
(1) Glycerine suppository
(2) Stimulant laxatives (e.g., bisacodyl)
(3) Enema
Rescue therapy
Constipation
symptoms
predominant
Function al
abdominal pain
predominant
Type of constipation?
Lifestyle modications (e.g., dietary bre, uid, and exercise)
Inadequate bre intake CIC, slow transit IBS-C Pelvic oor dyssynergic
defecation
History and physical examination including careful perineal/rectal examination
Assess alarm features Optimize management of secondary causes
Alarm features identied No alarm features identied Constipation persists
Specialist assessment
recommended (refer)
Patient education and management of expectations
Assess for complex or complicating features
Chronic Constipation Management Algorithm
e.g., linaclotide or prucalopride
Options as in slow
(e.g., stimulant,
osmotic laxative)
transit
titrate to ecacy and tolerability +/bre
F : Management algorithm for chronic constipation. e priority usage of each therapeutic option depends on patients’ tolerability and
aordability. 𝑇ℎ𝑒𝑟𝑒 has been no evidence to support the use of prucalopride in patients with IBS-C. (IBS-C:constipation-predominant irritable
bowel syndrome).
been shown to improve overall QoL and IBS symptoms
severity [–].
4.1.2. Treatment Recommendations Based on
Subtypes of Constipation
(1) Inadequate Fibre Intake. e recommended daily bre
intake is – g []. Fibre supplement helps increase
stool weight and improve stool consistency [] in order
to decrease stool transit time []. In patients with low
breintakebasedondietaryhistory,itislogicaltoadd
bre supplements. Soluble, such as psyllium, is preferable
overinsolublebrebecauseofthelowerpropensitytocause
associated abdominal symptoms (e.g., bloating or abdominal
pain); hence it is better tolerated by most patients []. e
recommended daily bre supplement intake is generally up
to  g per day []; the target consumption can be achieved
with gradual incremental increases (e.g.,  g/day increment
per week) to avoid side eects such as bloating and atulence.
(2) Chronic Idiopathic Constipation and Slow-Transit Consti-
pation. A thorough history and digital rectal examination
alongwiththeBristolStoolChartisfrequentlyadequateto
diagnose patients with slow-transit constipation. Type  or
 Bristol stool consistency correlates with prolonged colonic
transit time []. Although sitz marker colonic transit study
can be helpful, it is not widely accessible.
In patients with slow-transit constipation, osmotic lax-
atives are recommended as the rst-line pharmacological
agents to be used because of their eectiveness, accessibility,
and aordability. Milk of magnesia, lactulose, and PEG are
themostcommonlyusedosmoticlaxativesinCanada.Both
lactulose and PEG had randomized-controlled trials (RCTs)
to support their use [–] while milk of magnesia was
based on expert opinions and clinical experience [, ].
Milk of magnesia should not be used in patients with renal
impairment because of its renal excretion. In general, PEG
causes less bloating and atulence compared to lactulose; thus
it may result in better tolerability and compliance by patients.
If patients experience no improvement with their con-
stipation aer using osmotic laxatives, GCC agonist (lina-
clotide) or prokinetic agent (prucalopride) is recommended
as the second-line agent for regular use. Rescue therapy (i.e.,
Canadian Journal of Gastroenterology and Hepatology
T : Current recommended dosages of pharmacological agents for the treatment of constipation.
Typ e Age nt Do s e
Prosecretory agent Linaclotide  𝜇g oral daily (IBS-C);  𝜇goral
daily (CIC)
Fibre supplement Psyllium
 g daily or as tolerated; incremental
increases of -  g/week to achieve target
consumption
Prokinetic agent Prucalopride
mgoraldaily;dosereducestomgoral
daily in patients  years of age or renal
insuciency with creatinine clearance
 mL/min
Osmotic laxative
Lactulose – mL oral twice daily as needed
PEG   g/day as needed
Magnesium hydroxide– mL ( mg/mL) oral daily as
needed
Stimulant laxative
Sodium picosulfate  mg once daily
Senna .–. mg once daily
Bisacodyl – mg once dai ly
Avo id in patients with chronic renal insuciency.
glycerine suppository, stimulant laxatives, and enema) can
beaddedasadjuvanttherapyforoccasionaluse.Suppository
and enema are sometimes dicult for patients to administer.
ere is clinical opinion that stimulant laxatives could cause
dependency and cathartic colon if used regularly although
direct evidence to support this claim is unavailable.
An adequate trial of osmotic laxative use before stepping
up to the second-line agents varies depending on the ability to
provide follow-up in clinical practice. We recommend that if
a patient does not achieve a satisfactory response by  weeks,
therapy should be advanced to second-line agents such as
prucalopride or linaclotide. Eectiveness of linaclotide and
prucalopride in treating constipation has been proven in mul-
tiple placebo-controlled RCTs [–, –]. e commonly
reported side eect of linaclotide is diarrhea. In comparison,
prucalopride causes headache, nausea, abdominal pain, and
diarrhea in –% treated patients. is side eect prole
likely reects in the result of our survey that the respondents
found linaclotide most satisfactory in treating their patients
with constipation. Furthermore, in Canada, prucalopride is
only approved for use in woman with CIC; linaclotide is
approved for adults with CIC.
Stool soeners are not included in our management
algorithm because of weak evidence in supporting their use
[, ]. In fact, a multicenter double-blinded RCT involving
 patients for two weeks revealed inferiority of sodium
docusate compared to psyllium at improving stool frequency
[]. Probiotics are not included in the algorithm currently
due to insucient evidence to support their use [].
(3) IBS-C. A hallmark feature that distinguishes patients
diagnosed with IBS-C from CIC is the presence of associated
functional abdominal symptoms, namely, abdominal pain
and bloating. is has been consistently demonstrated in a
previous Canadian population study [] and in our current
survey. erefore, treatment agents that alleviate both consti-
pation and the associated debilitating functional abdominal
symptom would be preferable.
A GCC agonist, linaclotide, has been shown to improve
satisfactory complete spontaneous bowel movement fre-
quency and decrease associated abdominal pain [–]. Our
survey respondents also identied GCC agonist to be the
most satisfying in treating their patients with IBS-C. Hence,
the authors recommend linaclotide to be used as the rst-line
pharmacological agent in patients with IBS-C. e dosage of
linaclotide indicated for IBS-C is 𝜇gdailywhereasfor
CIC is  𝜇g daily (Table ).
Depending on the treatment response, supplemental
therapy such as stimulant laxatives and osmotic laxatives can
be used in patients requiring further treatment for consti-
pation, or neuropathic agents (selective serotonin reuptake
inhibitors, serotonin-norepinephrine reuptake inhibitors, tri-
cyclic antidepressants, or antispasmodics) in patients requir-
ing additional therapy for abdominal pain. It is worth not-
ing that tricyclic antidepressants and antispasmodics oen
worsen constipation. Nonpharmacological therapy such as
meditation, relaxation, or hypnosis has been shown to
improve functional abdominal symptoms in patients with IBS
[]. Patients who do not respond or are intolerable to the
treatment options outlined in the algorithm are suggested to
be referred to specialized centers for further assessment.
5. Conclusion
Our Canadian survey suggests that management strategies
for CIC and IBS-C among physicians are heterogeneous,
which can result in dissatisfaction in treatment response from
both patients and physicians. A management algorithm for
Canadian Journal of Gastroenterology and Hepatology
chronic constipation specically developed to apply in Cana-
dian practice will help in optimizing treatment outcomes for
patients suering from these functional GI disorders.
Appendix
Chronic Constipation Questionnaire
How would you describe your current work environ-
ment?
Academic
Community
Other: —
What is your current speciality?
General Surgery
GI specialist
Internal medicine
Family Practitioner
Other: —
Please identify any other role you have (select all that
apply)
Educator
Researcher
Administrator
Other: —
() How many patients with chronic constipation do you
see on a monthly basis?
None
◻<
–
–
–
–
+
() Do you generally follow a standard, graduated or
stepwise approach to the management of all patients
with constipation?
Yes
No
() In your experience, do you think that referring
physicians follow a standard, graduated or stepwise
approach to the management of patients with consti-
pation?
Yes
No
() Based on the type of chronic constipation, please
mark the order in which the patient would ideally
receive the following categories or treatment? Please
orderfrom16(1=rstchoice,6=lastchoice)
Inadequate bre intake
Stimulant laxatives ...
Stool soeners ...
Osmotic laxatives ...
Prokinetic (-HT agonist) ...
Fibre supplement/bulking agent ...
Pro-secretory Agent (GCC agonist) ...
Other agents ...
CIC, Slow Transit
Stimulant laxatives ...
Stool soeners ...
Osmotic laxatives ...
Prokinetic (-HT agonist) ...
Fibre supplement/bulking agent ...
Pro-secretory Agent (GCC agonist) ...
Other agents ...
CIC, Functional Outlet Obstruction (ie. Pelvic
oor dysfunction)
Stimulant laxatives ...
Stool soeners ...
Osmotic laxatives ...
Prokinetic (-HT agonist) ...
Fibre supplement/bulking agent ...
Pro-secretory Agent (GCC agonist) ...
Other agents ...
IBS-C
Stimulant laxatives ...
Stool soeners ...
Osmotic laxatives ...
Prokinetic (-HT agonist) ...
Fibre supplement/bulking agent ...
Pro-secretory Agent (GCC agonist) ...
Other agents ...
() Doyoufeelthereisreluctancetomovefromover-the-
counter therapies to prescription agents from:
(A) Patients
Yes
No
(B) Referring Physicians
Yes
No
()Howsatisedareyouwiththefollowingtreatment
options when managing patients with (A) CIC and
(B) IBS-C? ( being not satised,  being neutral, 
being very satised)
Canadian Journal of Gastroenterology and Hepatology
Stimulant Laxatives
Stool Soeners
Osmotic Laxatives
Prokinetic (-HT agonist)
Fibre supplement/bulking agent
Pro-secretory Agent (GCC agonist)
()Basedonthetypeofconstipation,pleaseidentify
which symptoms you feel most aect your patients
quality of life? (Order symptoms from –,  being the
most burdensome,  being the least)
CIC
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
IBS-C
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
() In your experience, which symptoms (if any) do
patients most oen complain about while on the
following therapy options? (Please select all that
apply)
Stimulant Laxatives
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
Stool Soeners
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
Osmotic Laxatives
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
Prokinetic (-HT agonist)
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
Fibre supplement/bulking agent
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
Pro-secretory Agent (GCC agonist)
Abdominal pain/bloating ...
Straining during bowel movements ...
Sensation of incomplete evacuation ...
Sensation of anorectal obstruction/block-
age ...
Infrequent stools ...
() Are you aware of the new ACG  recommen-
dations on the management of IBS-C and Chronic-
Idiopathic Constipation from ?
 Canadian Journal of Gastroenterology and Hepatology
Yes
No
(a) If yes, how useful are the ACG guidelines in
helping you prioritize how available agents are
used? ( being not useful,  being neutral, and 
being very useful)
(b) How valuable do you feel an evidence based
treatment algorithm that translates the ACG
guidelines into Canadian clinical practice would
be? ( being not valuable,  being neutral,  being
very valuable)
Competing Interests
Dr. Yvonne Tse has received honorarium for participation
in advisory boards from AbbVie. Dr. David Armstrong
has received research funding from AbbVie; honoraria for
participation in advisory boards and/or speaking at educa-
tional events from AbbVie, Allergan, Cubist, Ferring, Hos-
pira, Janssen, Lupin, Pendopharm, Pentax, Pzer, Shire, and
Takeda; sponsorship for educational events from AbbVie,
Allergan, Boston Scientic, Cook Medical, Ferring, Hospira,
Janssen, Lupin, Olympus, Pendopharm, Shire, and Takeda.
Dr. Christopher Andrews has received research funding
from Janssen and Allergan and honoraria from Allergan,
Pendopharm, Lupin, and AbbVie. Dr. Alain Bitton has
received honorarium for participation in advisory boards
from Allergan. Dr. Brian Bressler has received research
funding from AbbVie, Amgen, Takeda, BMS, Genentech,
Janssen, BI, GSK, Redhill Biopharm, Celgene, and Merck;
honoraria for participation in advisory boards and/or speak-
ing at educational events from AbbVie, Janssen, Takeda,
Shire, Pendopharm, Ferring, Pzer, Amgen, and Merck;
honoraria for providing consulting service from Genentech,
Pendopharm, and Allergan. Dr. John Marshall has received
honoraria for participation in speaking at educational events
from AbbVie, Allergan, Ferring, Janssen, Procter & Gamble,
Shire, and Takeda and honoraria for providing consulting
service from AbbVie, Allergan, Astra-Zeneca, Boehringer-
Ingelheim, Celgene, Celltrion, Ferring, Hospira, Janssen,
Merck, Pzer, Pharmascience, Procter & Gamble, Shire, and
Takeda. Dr. Louis Liu has received honoraria for participation
in advisory boards and/or speaking at educational events
from Takeda, AbbVie, Allergan, and Lupin and honorarium
for providing consulting service from Allergan.
Acknowledgments
e authors thank Converge and CARE for providing man-
agement, analytic, and research funds in support of this
Canadian National Survey project.
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... 139 First-line treatment for chronic constipation patients failing lifestyle modifications include fibre supplements or osmotic laxatives (such as PEG) on a regular basis, or stimulant laxatives intermittently, 50 which are available to patients as OTC products. 11,28,29,32,140 Indeed, many patients with chronic constipation will use some OTC laxative before consulting a health care provider. 141 Patients try an average of three OTC products before seeking help 141 ; however, only half feel satisfied. ...
... 7,141 Primary care providers should refer patients who are laxative refractory or intolerant to treatment to a gastroenterology provider for further assessment. 28,140 Primary care providers may try a promotility agent or prosecretory agent while awaiting gastroenterology evaluation. Gastroenterology providers may further titrate promotility agents or prosecretory agents and/or consider further testing-such as anorectal manometry, barium or magnetic resonance defecography, or colon transit time assessment-to identify F I G U R E 4 Management algorithm for the treatment of constipation. ...
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Background: Chronic constipation is a common, heterogeneous disorder with multiple symptoms and pathophysiological mechanisms. Patients are often referred to a gastroenterology provider after laxatives fail. However, there is limited knowledge of the spectrum and management of constipation disorders. Aim: To discuss the latest understanding of the spectrum of constipation disorders, tools for identifying a pathophysiologic-based diagnosis in the specialist setting, treatment options and the patient's perspective of constipation. Methods: Literature searches were conducted using PubMed for constipation diagnostic criteria, diagnostic tools and approved treatments. The authors provided insight from their own practices. Results: Clinical assessment, stool diaries and Rome IV diagnostic criteria can facilitate diagnosis, evaluate severity and distinguish between IBS with constipation, chronic idiopathic constipation and dyssynergic defecation. Novel smartphone applications can help track constipation symptoms. Rectal examinations, anorectal manometry and balloon expulsion, assessments of neuromuscular function with colonic transit time and colonic manometry can provide mechanistic understanding of underlying pathophysiology. Treatments include lifestyle and diet changes, biofeedback therapy and pharmacological agents. Several classes of laxatives, as well as prokinetic and prosecretory agents, are available; here we describe their mechanisms of action, efficacy and side effects. Conclusions: Constipation includes multiple overlapping subtypes identifiable using detailed history, current diagnostic tools and smartphone applications. Recognition of individual subtype(s) could pave the way for optimal, evidence-based treatments by a gastroenterology provider.
... 1,2 Although constipation is not a deadly and debilitating disorder, it has a high impact on quality of life, requiring frequent medical attention in most patients. [2][3][4][5] Chronic constipation can be either primary or secondary to other neurological, metabolic, and endocrine diseases. 6 Primary constipation is categorized into three types: slow-transit constipation, fecal evacuation disorder (FED), and constipation-predominant irritable bowel syndrome (IBS) with normal transit. ...
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Background Functional evacuation disorder (FED) is the second most common cause of functional constipation (FC) after constipation-predominant irritable bowel syndrome. However, the data on FED is relatively scanty in our region. Hence, the present study was performed to evaluate the demographics of FED and to find out the predictors of FED in patients with chronic constipation. Methods A total of 134 patients with chronic constipation diagnosed according to the Rome IV criteria who were referred for high-resolution anorectal manometry (HRAM) were retrospectively enrolled in the present study. All FC patients who underwent HRAM were asked to fill a questionnaire and underwent anorectal manometry and were submitted to the balloon expulsion test (BET). Results The mean age of patients was 43.09 ± 9.32 years old, with a total of 76 (54%) males. The most common symptom was straining during defecation (87%) followed by incomplete evacuation (86%). The prevalence of FED, diagnosed by HRAM and by the BET was 39%. Patients with FED had a significantly higher percentage of straining and sensation of anorectal blockade compared with those without FED (96 versus 82%; p < 0.01; 81 versus 44%; p < 0.001, respectively). On the multivariate regression analysis, straining > 30 minutes (odds ratio [OR] = 3.63; p = 0.03), maximum squeeze pressure (OR = 1.05; p < 0.001), and balloon volume at maximal sensation (OR = 1.06; p < 0.001) were found to be significant independent predictors of FED. Conclusion Prolonged straining and sensation of anorectal blockade were significant indicators of FED in patients with chronic constipation.
... Regular use of stimulant laxatives can cause dependency and cathartic colon albeit there is no direct evidence to support this claim. 75 Prolonged use of stimulant laxatives leaves users prone to drug dependence, malabsorption, and electrolyte imbalance, and can damage the enteric nervous system, weakening colonic strength and even giving rise to melanosis coli. Moreover, long-term use of stimulant laxatives can damage the myenteric plexus, reducing responsiveness of the colon to intestinal contents and weakening colonic motor function. ...
Article
Constipation is a commonly reported disorder in many patients. Constipation treatment using laxatives on a regular and long term basis can lead to patient dependence, especially among the elderly. However, there is scanty data on the habit-forming potential of laxatives in Indian constipated patients. This review has explored literature evidence and expert opinion on patients’ experience regarding habit-forming attributes of stimulant and osmotic laxatives. Additionally, structured face-to-face discussions were conducted with 2 key opinion leaders to understand their clinical experience on the habit-forming aspects stimulant and osmotic laxatives in patients with constipation. Based on literature evidence, lactulose is not known to lead to any habit-forming behaviors in patients. Furthermore, experts pointed out that dependence on stimulant laxatives is common, but not on osmotic laxatives, and emphasized that milk of magnesia is not habit forming. In conclusion, no habit-forming characteristics or dependence was observed with the use of osmotic laxatives in India. Nevertheless, real-world, studies exploring patient and physician perspectives are warranted to establish the dependence and habit forming attributes of laxatives.
... 48,67 Moreover, prucalopride was reportedly used rather frequently in clinical practice among Canadian and Italian gastroenterologists for IBS-C patients in two recently conducted surveys. 76,77 Further studies regarding this crucial clinical issue are required. ...
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Prucalopride is a third-generation, highly selective 5-hydroxytryptamine 4 (5-HT4) receptor agonist. Many recent studies indicate prucalopride may play an important role in various motility disorders. The aim of this study was to investigate safety and patient selection considerations when using prucalopride as gastroparesis and chronic constipation treatment. We systematically searched PubMed, Embase, the Cochrane Central Register and ClinicalTrials.gov, and we reviewed all studies that evaluated prucalopride for the treatment of gastroparesis and chronic idiopathic constipation in adults. Prucalopride is an effective and safe option based on all the studies currently conducted. Thus, it may be the first-line treatment in the future. Prucalopride has the potential to be useful in the treatment of functional constipation and other forms of gastrointestinal diseases (eg, gastroparesis). Through the research on this potential, prucalopride is expected to be a useful and versatile option for treating gastrointestinal diseases in the future.
... Guidelines for treating IBS-C and CIC generally recommend a shift toward prescription medications if symptom control is not achieved with lifestyle modifications and/or OTC treatments. 23,[25][26][27] Despite this, few patients with IBS-C/CIC are on prescription therapyonly 1 in 3 (36%) CONTOR participants, congruent with the 12% to 35% range found in previous analyses 9,10,18 -even though many reported persistent burdensome symptoms. Together with findings that prescription medications are associated with higher treatment satisfaction and reduced healthcare resource utilization and costs, [28][29][30] our results suggest some IBS-C/CIC patients may benefit from these treatments but do not receive them. ...
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Aims: To characterize a US population of patients with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) using CONTOR, a real-world longitudinal research platform that deterministically linked administrative claims data with patient-reported outcomes data among patients with these conditions. Methods: Patients with IBS-C or CIC were identified using diagnosis and treatment codes from administrative claims. Potential respondents received a mailed survey followed by 12 monthly online follow-up surveys and 2 mailed diaries. Surveys collected symptom severity, treatment use, quality of life, productivity, and condition/treatment history. Comorbidities and healthcare costs/utilization were captured from claims data. Diaries collected symptoms, treatments, and clinical outcomes at baseline and 12 months. Data were linked to create a patient-centric research platform. Results: Baseline surveys were returned by 2,052 respondents (16.8% response rate) and retention rates throughout the study were high (64.8%–70.8%). Most participants reported burdensome symptoms despite having complex treatment histories that included multiple treatments over many years. More than half (55.3%) were dissatisfied with their treatment regimen; however, a higher proportion of those treated with prescription medications were satisfied. Limitations: The study sample may have been biased by patients with difficult-to-treat symptoms as a result of prior authorization processes for IBS-C/CIC prescriptions. Results may not be generalizable to uninsured or older populations because all participants had commercial insurance coverage. Conclusions: By combining administrative claims and patient-reported data over time, CONTOR afforded a deeper understanding of the IBS-C/CIC patient experience than could be achieved with 1 data source alone; for example, participants self-reported burdensome symptoms and treatment dissatisfaction despite making few treatment changes, highlighting an opportunity to improve patient management. This patient-centric approach to understanding real-world experience and management of a chronic condition could be leveraged for other conditions in which the patient experience is not adequately captured by standardized data sources.
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Background: The estimated prevalence of bloating is 15 to 30% in the adult US population and is even higher in patients with disorders of gut-brain interaction (DGBIs). Despite this frequency, there is little research into patients who endorse bloating as a predominant symptom. The aim of this study was to better characterize these patients. Materials and methods: New patients with DGBIs were asked to identify their 3 most predominant symptoms over the preceding 3 months; those who reported bloating were classified as "bloating predominant." Rome IV and symptom-specific questionnaires were administered to assess for the frequency of DGBIs and other predominant symptoms in this patient population. Using univariable and multivariable modeling, we analyzed the associations between bloating predominance, DGBI subtype, and clinical characteristics. Results: Of the 586 patients surveyed, 242 (41%) reported predominant bloating. Bloating-predominant patients were more likely to be female, younger, and meet the criteria for IBS-mixed (IBS-M), functional constipation, and functional dyspepsia compared with nonbloating-predominant patients. Bloating-predominant patients were also more likely to endorse concurrently predominant constipation, incomplete evacuation, abdominal pain, belching, and/or nausea. On multivariable logistic regression, constipation and abdominal pain severity were positively associated, although depression was negatively associated with predominant bloating. Conclusions: Patients with predominant bloating are more likely to have constipation-related symptoms than diarrhea-related symptoms. They are also more likely to have more severe abdominal pain than patients without predominant bloating. These findings help characterize patients with bloating as a predominant symptom and suggest that diagnosing and treating constipation should be considered as first-line treatment.
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Patients with chronic idiopathic constipation and irritable bowel syndrome with constipation experience an array of gastrointestinal symptoms. Given the subjective nature of these disorders, patient self-reporting is critical to diagnosis and monitoring response to therapy. Unfortunately, many patients are reluctant to discuss bowel symptoms with their healthcare providers. Differences in sex, health literacy, and age can influence symptom reporting. Negative patient-physician relationships and dissatisfaction with care lead patients to seek alternative treatments, switch healthcare providers, or discontinue care. Thus, adopting a patient-centered communication style can help create a shared understanding of patients' symptoms, achieve accurate symptom reporting, expedite diagnosis, and facilitate appropriate treatment plans. Currently, there are multiple symptom and quality-of-life scales available to assist healthcare providers in this endeavor. These scales also allow for the monitoring of constipation-related symptoms and symptom severity. When using patient self-assessments to measure treatment responses, scale selection may depend on the number of symptoms being assessed, the duration and frequency of assessments, and patients' comprehension and language skills.
Chapter
This article addresses the management of chronic constipation and opioid-induced constipation. Apart from increasing dietary fiber, there are several classes of medications that can be used for treatment of constipation, and these include osmotic and secretory laxatives, agents that impede the re-absorption of endogenous bile acids resulting in stimulation of motor and secretory functions in the colon, and agents that stimulate the motor function of the colon thereby propelling stool towards the rectum. Several drug classes are also available for the treatment of opioid-induced constipation including peripherally active mu-opioid receptor antagonists, and some of the same secretory agents and prokinetics that are used for chronic constipation. For both of these indications, there have recently been studies that compared efficacy and safety of the available drugs through network meta-analyses, which are also summarized in this article.
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Food is considered as important environmental factor that plays a role in development of Hashimoto's thyroiditis (HT). The goal of our study was to identify food groups, assessed by food frequency questionnaire, that differ in consumption frequency between 491 patients with HT and 433 controls. We also analysed association of food groups with the wealth of HT-related clinical traits and symptoms. We found significantly increased consumption of animal fat (OR 1.55, p < 0.0001) and processed meat (OR 1.16, p = 0.0012) in HT cases, whereas controls consumed significantly more frequently red meat (OR 0.80, p < 0.0001), non-alcoholic beverages (OR 0.82, p < 0.0001), whole grains (OR 0.82, p < 0.0001) and plant oil (OR 0.87, p < 0.0001). We also observed association of plant oil consumption with increased triiodothyronine levels in HT patients (β = 0.07, p < 0.0001), and, association of olive oil consumption with decreased systolic blood pressure (β = − 0.16, p = 0.001) in HT patients on levothyroxine (LT4) therapy. Analysis of food consumption between HT patients with and without LT4 therapy suggest that patients do not tend to modify their diet upon HT diagnosis in our population. Our study may be of relevance to nutritionists, nutritional therapists and clinicians involved in developing dietary recommendations for HT patients.
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New pharmacological therapeutics are needed to achieve substantial relief of constipation symptoms and normalization of gastrointestinal motility. In recent years, several new agents with novel mechanisms of action that are both efficacious and safe have been approved in Japan for the treatment of chronic constipation. Osmotic laxatives, such as polyethylene glycol (PEG) and lactulose, contain poorly absorbed molecules that draw water into the intestinal lumen, thus softening stool and increasing intestinal transit. A systematic review found that PEG was superior to both placebo and lactulose in adults and children. The most common adverse events for PEG include distension and diarrhea, whereas lactulose commonly causes dose-dependent abdominal cramping and bloating. Lubiprostone stimulates chloride secretion through activation of type-2 chloride channels, increasing intestinal secretion and transit, and its use has been associated with improvements in bowel habit and symptoms of constipation. Nausea and diarrhea are the most commonly reported adverse events. Linaclotide is a minimally absorbed agonist of guanylate cyclase-C that reduces symptoms associated with irritable bowel syndrome with constipation. Elobixibat exerts its novel mechanism of action by blocking the ileal absorption of bile acids, which ultimately increases the flow of bile into the colon, causing increased intestinal secretions and transit.
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Despite existing evidence-based practice guidelines for the management of acute pancreatitis, clinical compliance with recommendations is poor. We conducted a retrospective review of 248 patients admitted between 2010 and 2012 with acute pancreatitis at eight University of Toronto affiliated hospitals. We included all patients admitted to ICU (52) and 25 ward patients from each site (196). Management was compared with the most current evidence used in the Best Practice in General Surgery Management of Acute Pancreatitis Guideline. Fifty-six patients (22.6 %) had only serum lipase tested for biochemical diagnosis. Admission ultrasound was performed in 174 (70.2 %) patients, with 69 (27.8 %) undergoing ultrasound and CT. Of non-ICU patients, 158 (80.6 %) were maintained nil per os, and only 18 (34.6 %) ICU patients received enteral nutrition, commencing an average 7.5 days post-admission. Fifty (25.5 %) non-ICU patients and 25 (48.1 %) ICU patients received prophylactic antibiotics. Only 24 patients (22.6 %) with gallstone pancreatitis underwent index admission cholecystectomy. ERCP with sphincterotomy was under-utilized among patients with biliary obstruction (16 [31 %]) and candidates for prophylactic sphincterotomy (18 [22 %]). Discrepancies exist between the most current evidence and clinical practice within the University of Toronto hospitals. A guideline, knowledge translation strategy, and assessment of barriers to clinical uptake are required to change current clinical practice.
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The irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are associated with substantial symptom and disease burden. Although typically classified as distinct diseases, symptoms frequently overlap. The objective of this study was to characterize symptom and disease burden in IBS-C and CIC sufferers and examine a subset of CIC sufferers with abdominal symptoms. In a US population-based survey, respondents meeting the Rome III criteria for IBS-C or CIC rated symptom frequency and bothersomeness, missed work and disrupted productivity, and degree of obtaining and satisfaction with physician care. CIC respondents were analyzed in two subgroups: those with abdominal symptoms ≥once weekly (CIC-A) and those without (CIC-NA). Of the 10,030 respondents, 328 met the criteria for IBS-C and 552 for CIC (363 CIC-A; 189 CIC-NA). All symptoms were significantly more frequent in IBS-C vs. CIC respondents (P<0.0001). Constipation was extremely/very bothersome in 72% of IBS-C respondents, 62% of CIC-A, and 40% of CIC-NA (P<0.01 all pairs). All 11 other measured symptoms were significantly more bothersome in IBS-C and CIC-A vs. CIC-NA respondents. In IBS-C vs. CIC-A, abdominal discomfort, bloating, straining, and pellet-like stools were also significantly more bothersome, with other remaining symptoms similar. Gastrointestinal symptoms disrupted productivity a mean of 4.9 days per month in IBS-C respondents, 3.2 in CIC-A, and 1.2 in CIC-NA (P<0.001 all pairs); missed days were similar in IBS-C and CIC-A respondents. CIC respondents with abdominal symptoms experience greater disease burden compared with CIC respondents without frequent abdominal symptoms and have a disease burden profile that is similar to IBS-C respondents.Am J Gastroenterol advance online publication, 17 March 2015; doi:10.1038/ajg.2015.67.
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The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)
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Chronic constipation is a common functional gastrointestinal disorder that affects patients of all ages. In 2007, a consensus group of 10 Canadian gastroenterologists developed a set of recommendations pertaining to the management of chronic constipation and constipationdominant irritable bowel syndrome. Since then, tegaserod has been withdrawn from the Canadian market. A new, highly selective serotonin receptor subtype 4 agonist, prucalopride, has been examined in several large, randomized, placebo-controlled trials demonstrating its efficacy and safety in the management of patients with chronic constipation. Additional studies evaluating the use of stimulant laxatives, polyethylene glycol and probiotics in the management of chronic constipation have also been published. The present review summarizes the previous recommendations and new evidence supporting different treatment modalities – namely, diet and lifestyle, bulking agents, stool softeners, osmotic and stimulant laxatives, prucalopride and probiotics in the management of chronic constipation. A brief summary of lubiprostone and linaclotide is also presented. The quality of evidence is presented by adopting the Grading of Recommendations, Assessment, Development and Evaluation system. Finally, a management pyramid for patients with chronic constipation is proposed based on the quality of evidence, impact of each modality on constipation and on general health, and their availabilities in Canada.
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Digital rectal examination (DRE) is a simple clinical method to diagnose anorectal disorders. High-resolution antorectal manometry (HRAM) based on a spatiotemporal plot is expected to promote improved diagnostic accuracy. However, there are no reports comparing the effectiveness of DRE and HRAM. The aim of our study was therefore to evaluate the diagnostic value of DRE compared with HRAM. A total of 309 consecutive patients with chronic constipation (n=268) or fecal incontinence (n=41) who underwent a standardized DRE, HRAM, and balloon expulsion test were enrolled in this study. The diagnostic yield of DRE compared with HRAM was determined, and agreement between DRE and HRAM data was evaluated. Of the constipated patients, 207 (77.2%) were diagnosed with dyssynergia using HRAM. The sensitivity, specificity, and positive predictive value of DRE in the diagnosis of dyssynergia were 93.2%, 58.7%, and 91.0%, respectively, and moderate agreement was seen between the two modalities (κ-coefficient =0.542, P<0.001). In patients with fecal incontinence, there was moderate agreement in terms of anal squeeze pressure between the two modalities (κ-coefficient =0.418, P=0.006); however, there was poor agreement for anal resting tone (κ-coefficient =0.079, P=0.368). DRE shows high sensitivity and positive predictive value in detecting dyssynergia compared with HRAM, and could therefore be used as a bedside screening test for the diagnosis of this disorder. Further studies are warranted to evaluate the correlation between DRE and HRAM in assessing anal sphincter pressure.Am J Gastroenterol advance online publication, 2 June 2015; doi:10.1038/ajg.2015.153.
Article
AIMS—To assess the long term therapeutic effectiveness, safety, and tolerability of low daily doses of isosmotic PEG electrolyte solutions (PMF-100) administered for a six month period for the treatment of functional constipation, in a double blind, placebo controlled, parallel group study. METHODS—After an initial four week run in period with PMF-100 (250 ml twice daily; PEG 14.6 g twice daily), 70 patients suffering from chronic constipation (58 females, aged 42 (15) years) with normalised bowel frequency (>3 bowel movements (bm)/week) were randomly allocated to receive either PMF-100 or placebo, contained in sachets (one sachet in 250 ml of water twice daily) for 20 weeks. Patients were assessed at four week intervals, and reported frequency and modality of evacuation, laxative use, and relevant symptoms on a diary card. At weeks 1, 12, and 24, a physical examination and laboratory tests were performed. RESULTS—Complete remission of constipation was reported by a significantly (p<0.01) higher number of patients treated with PMF-100 compared with placebo at each four week visit. At the end of the study, 77% of the PMF-100 group and 20% of the placebo group were asymptomatic. Compared with placebo, patients treated with PMF-100 reported hard/pellety stools and straining at defecation less frequently, a significantly higher bowel frequency (week 12: 7.4 (3.1) v 4.3 (2.5) bm/week, 95% CI 1.64, 4.42; week 24: 7.4 (3.2) v 5.4 (2.1) bm/week, 95% CI 0.13,3.93), reduced consumption of laxative/four weeks (week 12: 0.7 (2.7) v 2.2 (3.3), 95% CI −2.29, 0.03; week 24: 0.2 (0.8) v 1.4 (2), 95% CI −2.07, −0.023), reduced mean number of sachets used (week 12: 33 (13) v 43 (12), 95% CI −17.24, 4.56; week 24: 33 (13) v 44 (12), 95% CI −19.68, −2.24), and reduced number of drop outs for therapy failure (16 v 3; p<0.005). Adverse events, physical findings, laboratory values, palatability, and overall tolerance of the solutions did not differ between groups. CONCLUSIONS—Administration of small daily doses of isosmotic PEG electrolyte balanced solutions was effective over a six month period for the treatment of functional constipation. A mean daily dose of approximately 300 ml of PEG solution (PEG 17.52 g) appeared to be safe, well tolerated, and devoid of significant side effects. Keywords: constipation; polyethylene glycol; safety; tolerability
Article
Anorectal disorders such as dyssynergic defecation, fecal incontinence, levator ani syndrome, and solitary rectal ulcer syndrome are common, and affect both the adult and pediatric populations. Although they are treated with several treatment approaches, over the last two decades, biofeedback therapy using visual and verbal feedback techniques has emerged as an useful option. Because it is safe, it is commonly recommended. However, the clinical efficacy of biofeedback therapy in adults and children is not clearly known, and there is a lack of critical appraisal of the techniques used and the outcomes of biofeedback therapy for these disorders. The American Neurogastroenterology and Motility Society and the European Society of Neurogastroenterology and Motility convened a task force to examine the indications, study performance characteristics, methodologies used, and the efficacy of biofeedback therapy, and to provide evidence-based recommendations. Based on the strength of evidence, biofeedback therapy is recommended for the short-term and long-term treatment of constipation with dyssynergic defecation (Level I, Grade A), and for the treatment of fecal incontinence (Level II, Grade B). Biofeedback therapy may be useful in the short-term treatment of Levator Ani Syndrome with dyssynergic defecation (Level II, Grade B), and solitary rectal ulcer syndrome with dyssynergic defecation (Level III, Grade C), but the evidence is fair. Evidence does not support the use of biofeedback for the treatment of childhood constipation (Level 1, Grade D). © 2015 John Wiley & Sons Ltd.