N/V/D/C/IBS Flashcards
(115 cards)
1
Q
N/V causes?
A
GI irritation, motion sickness, vestibular dz, hormone imbalance, drugs and radiation, exogenous toxins, pain, psychogenic factors, intracranial pathology
2
Q
N/V clinical presentation?
A
everyone aware of. dehydration can occur: inc. thirst and dry mouth, less frequent urination, tachycardia, pinching skin takes longer to go down (dec. turgor)
3
Q
What is the N/V non-pharm tx?
A
rehydrate (ORS = oral rehydration solutations), avoid dairy, BRAT diet 24 hrs. after fluid only (banana, rice, apple sauce, toast dry)
4
Q
What are the types of N/V Pharmacologic tx?
A
- 5-HT3 Antagonists
- Dopamine Antagonists
- Antihistamines
- Cannabinoids
5
Q
What are the 5-HT3 Antagonists and how do they work?
A
Ondansetron (Zofran) used Granisetron (Kytril) Dolasetron (Anezmet) MOA: antagonism of the 5-HT4 receptor in the chemo-receptor trigger zone (CTZ) Route: PO, PR, IM, IV
6
Q
What are the 5-HT3 Antagonists indications and ADRs?
A
Indications: tx and prevention of postoperative N/V, chemo-induced N/V
ADRs: HA (common), dizziness, diarrhea, abdo pain
7
Q
What are the Dopamine Antagonist and how do they work?
A
Metoclopramide (Reglan)
Trimethobenzamide (Tigan)
Phenothiazine (Prochlorperazine - Compazine)
MOA: antagonist of D2 receptors in CTZ, at higher doses metoclopramide also block 5-HT3 receptors. Also promotes gastric emptying and small intestine peristalsis = prokinetic effects!!!
8
Q
What are the Dopamine Antagonists CIs and ADRs?
A
CI: GI - hemorrhage, obstruction or perf (d/t prokinetic effects), caution in pts w/depression, pheochromocytoma, seizure, caution in kids
ADRs: extrapyramidal effects (d/t blocking DA - parkinson-like effects), restlessness, anxiety, drowsiness, fatigue, hallucinations, CV: HTN, HPOTN, AV block, bradycardia, agranulocytosis
9
Q
Name the types of Antihistamines and how they work?
A
Promethazine (Phenergan), Phenothiazine
MOA: blocks H1 –> effectiveness appears to be w/motions sickness and vestibulocochlear dz, antagonist of D2 receptors in the CTZ.
Dose: 12.5-25 mg Q4hr. PRN, IV, PO, PR (MUST be diluted with NS for injection, dangerous in extravasation)
10
Q
What are the ADRs and cautions for Antihistamines
A
ADRs: dry mouth, dizziness, Parkinsonian symptoms (dyskinesia, dystonias, akathisia, neuroleptic malignancy syndrome (life threatening), blood dyscrasias. Caution in BPH, urinary retention, glaucoma
11
Q
Cannabinoids can be used to treat N/V and what is it called/side effects, etc?
A
Dronabinol (Marinol), MOA not well defined.
Side effects: drowsiness, sedation, inc. appetite
12
Q
What is normal motility of the intestines called and what does it do?
A
peristalsis, acts to mix bowel contents thorougly, to propel them in the caudal direciton
13
Q
Regulation of normal intestinal motility is under control of what?
A
neuronal and hormonal
14
Q
What classes of drugs are used to affect GI motility
A
laxatives, antidiarrheal agents, prokinetic agents, antiemetic agents, antispasmodics
15
Q
What is the definition of constipation
A
2 or more of: straining >25% of time, lumpy/hard stools >25% of time, feeling of incomplete evacuation >25% of time, 2 or fewer BM in 1 week
16
Q
What are some causes of conatipaiton?
A
Metabolic: hypothyroid, hypercalcemia, hypokalemia
GI disorder: tumors, IBS, diverticulitis
Pregnancy
Neurogenic: trauma to brain/spinal cord, CNS tumor, Parkinson’s
17
Q
What are some meds that cause constipation
A
Opiates (most), Ca and Al antacids, Fe, Ca++ channel blockers (Verapamil), Clonidine, Anticholinergics (antihistamines, antiparkinsonians, TCA)
18
Q
What are some non-pharm tx/management/prevention of constipation
A
drink plenty of H20/fluids, “P” jucies, adequate exercise, high fiber diet including: insoluble - shorten intestinal transit time and inc. stool bulk (whole grains/bran); water soluble fiber: more moist stool and less effect on transit time (fresh fruits/veggies)
19
Q
What are laxatives used for?
A
hasten transit time in the gut and encourage defecation. Also used to clear bowel prior to medical and surgical procedures
20
Q
What are the laxatives from lecture?
A
bulk-forming laxatives emollients and lubricants saline cathartics osmotic laxatives stimulant laxatives
21
Q
What are the bulk forming laxatives?
A
Psyllium (Metamucil)
Methylcellulose (Citrucel)
Polycarbophil (Fibercon)
22
Q
What is the MOA of bulk-forming laxatives and their onse?
A
inc. volume of non-absorbable solid residue w/water, distending colon and stimulating peristaltic activity, inc. rate of colonic transit . adequate fluid intake is important while taking these. onset: 2-3 days?
23
Q
For which type of patients are bulk-forming laxatives considered first line? What are some CIs?
A
bedridden or geriatric w/chronic constipation. also good in pregnancy
CI: pts w/stenosis, ulceration or adhesions, fecal obstruction
24
Q
What are the ADRs and DIs for bulk-forming laxatives?
A
ADRs: flatulence, abdo distention, gastro obstruction
DI: binds to drugs and reduces absorption - separate from other meds
25
What are some other uses of bulk-forming laxatives
ability of these agents to absorb H20 makes them useful for relieving sxs of mild diarrhea, several months use can relieve sxs of irritable bowel syndrome, lowering cholesterol.
26
What is the emollient from lecture and what is the indication?
```
Docusate sodium (Colace). Indication: to avoid straining, after MI, surgery, opiates
FIRST LINE pregnant women (also bulk-forming laxatives)
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27
What is the MOA, onset and CIs for emollients (Docusate sodium - Colace?)
onset 1-3 days
MOA: surfactant brings H20 into stool, facilitates mixing of aqueous and fatty materials within intestines, increase H20 and electrolyte secretion in small/large bowel.
CI: fecal impaction, s/sx of appendicitis
28
Mineral oil is what? and used for?
a lubricant - chronic use is discouraged!, mainly used to avoid straining, after Mi, rectal surgery
29
What is the onset time, MOA and caution, for lubricants (mineral oil)?
6hr-3 days (PO or PR)
MOA: coats stool (allows easier passage), inhibits colonic absorption of H20
caution: avoid in elderly, aspiration risk and dec. absorption of fat-soluble vitatmins (DEAK) - may leak from anal sphincer.
30
What are the osmotic agents?
Lactulose and Sorbitol
31
What is the MOA and indication for Lactulose (osmotic agent)?
MOA: disaccharide that is metabolized by bacteria in colon to low-molecular weight acids = osmotic effect (so pulling in fluid). NOT considered 1st line agent. May result in flatulent, cramps. electrolye imbalances. More commonly used in pts w/hepatic encephalopathy. PO softens stools in 1-3 days
32
What is MOA for Sorbitol (osmotic agent)
MOA: monosaccharide creates osmotic gradient when used as a 70% solution, hyperglycemia. PO dose softens stool in 1-3 days
33
What are the types of saline cathartics?
Magnesium hydroxide (MOM), Magnesium sulfate (epsom salts), sodium phosphate (Fleets enema), Magnesium citrate (citrate of Magnesia)
34
What is the MOA/CI/onset for saline cathartics?
onset: 30min-6hr. PO, 5-30min. PR (enema)
MOA: Mg++ or Na+ salts are poorly absorbed; they inc. the H20 content of the bowel through osmosis.
CI: impaired renal fxn. Mg and Na accumulation, CHF, no sodium for HTN pts
35
What is the MOA for Castor Oil?
MOA: metabolized to ricinoleic acid - stimulates secretory pathways.
Decreased glucose absorption, promotes intestinal motility. NOT for routine use.
36
What is the MOA/onset for glycerin suppository?
MOA: osmotic action in rectum
onset:
37
What are the two types of Glycerin/Hyperosmotic agents?
```
Polyethylene glycol (Miralax)
and Polyethylene glycol (PED, GoLYTELY)
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38
How do you use Miralax (Polyethylene glycol)
17g mixed w/water or juice, usually 2 weeks duration, chronic use OK!!
onset: 1-3 days (Miralax)
MOA: osmotic
Note: relatively safe, OK in kids!
39
What is the other use for the Polyethylene glycol (PED, GoLYTELY)? and how is it used/onset etc.?
used for colonic cleansing before diagnostic procedures.
onset: 1 hr. after initiation
MOA: osmotic agent that causes retention of H20 resulting in softer stool and more frequent defecation.
Note: 4 L over 3 hrs (8 oz glass q10min) NOT for chronic use!! Avoid in patients with intestinal obstruction!!!
40
What are the stimulant laxatives
Diphenylmethane Derivations - Bisacodyl (Dulcolax)
| Anthraquinone Laxatives - Senna (Senokot)
41
What is the MOA of Bisacodyl (Dulcola) (it's a diphenylmethane derivative, stimulant laxative)
stimulate nerve plexus of colon (>12 yr oral: 5-30mg Qday; rectally: Qday) onset: 6-8 hr (PO); 1-6 (PR). DON'T take w/in 1 hour of antacids, milk or milk products
42
What are the ADRs and long term effects of Bisacodyl (Dulcolax)?
ADRs: intestinal cramps, can cause fluid and electrolyte imbalance, PINK colored urine and feces
Long term use: could cause damage to nerve plexi, resulting in deterioration of intestinal function --> atonic colon!
43
What is the MOA for the Anthraquinone Laxative Senna (Senokot)? (it's a stimulant laxative)
MOA: increased peristalsis. Co-formulated w/docusate (Senokot-S)
>12 yrs: 1-4 tabs Qday - NOT rec
44
What are teh ADRs, long term effects and CI of Senna (Senokot) an anthraquinone laxative (stimulant laxative type)
ADRs: yellow-brown to red colored urine, large doses can produce nephritis
Long-term use: could damage the nerve plexi, leading to deterioration of intestinal function, atonic colon
CI: PREGNANCY and acute intestinal inflammation!!!
45
What is the MOA and side effects/CI of Lubiprostone (Amitiza)
```
MOA: chloride-channel activator, works by inc. fluid secretion locally in the small intestine by activating the ClC-2 chloride channel
Side effects: N/D
onset: 1d-1 week+
CI: intestinal obstruction, pregnancy
USED for opiate-induced C.
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46
What is the MOA of Methylnaltreoxone?
MOA: peripherally acting antagonist of mu. Does not cross BBB, reduces effects of opiods of periphery, NOT centrally.
Renal dose adjustmend for CrCl
47
What should you use for diabetic patients with constipation?
60% have C, doesn't cause inc. in mortality. Use sugar-free products (Metamucil) also don't want to give things that are hard on kidneys b/c DM and kidney dz usually go hand-in-hand
48
What should you use for pregnancy women with C?
use bulk formers or emollients. AVOID mineral oil, castor oil and osmotics.
1 in 3 women experience C.
49
What should you use for opiate users with C?
exercise, adequate fluid, fiber
50
What should you use for elderly patients with C?
bulk-forming laxatives, enemas, glycerin, lactulose (especially for bed ridden pts), "P" juices, best to avoid saline laxative d/t potential changes in electrolytes
51
What should you use in kids with C?
usually d/t dietary habits, "P" juices,
52
What is the difference between acute and chronic diarrhea?
acute: 14 days. Most don't seek medical tx. Usually healthy response -- don't use symptomatic txs too early
53
When should you NOT use antimotility agents?
If dysentery or C. diff is possible!!!!
54
Acute diarrhea is mostly what??
infectious and self limiting. deadly in many parts of work d/t dehydration!
55
What does the Rotavirus cause?
watery D lasting 3-7 days, 1/3 have fever, nearly every child in US affected by 5. Vaccine (RotaTeq) approved in 2006, given at 2, 4 and 6 mos. old
56
What are the 4 clinical groups of diarrhea?
Secretory: excess H20 and electrolytes
Osmotic: substances that draw intestinal fluid
Exudative: d/t inflammatory dz of GI
Altered intestinal transit
57
What is secretory diarrhea?
A stimulating substance either increases secretion or decreases absorption of large amounts of H20 and electrolytes.
Clinically recognized by large stool volume >1L/day w/normal ionic contents/osmolality.
58
Does fasting alter the stool volume with secretory diarrhea?
No, if the pt fasts, the volume will still be large! (>1 L/day)
59
What is osmotic diarrhea?
Poorly absorbed substanes lead to retention of intestinal fluids --> diarrhea.
60
Does fasting alter osmotic diarrhea?
Yes, it is clinically recognized if the diarrhea STOPS when patient does not eat!
61
What is exudative diarrhea?
Inflammatory diseases that discharge mucus, serum proteins and blood into gut.
62
What are some way the intestinal transit time can be altered?
1. Reduced contact time in small intestine -- intestinal resection or bypass surgery 2. premature emptying colon -- Metoclopramide, Erythromycin 3. Bacterial overgrowth -- inc. time of exposure can lead to bacterial overgrowth.
63
What are some causes of drug induced diarrhea?
Laxatives, antacids containing Mg, Antineoplastics, Colchicine, NSAIDs, Orlistat, Antibiotics: Clindamycin, Broad spectrum abx, antiHTNsives: ACEI, cardiac agents: Digoxin, PPIs: esomeprazole, H2 blockers: Famotidine
64
What is the presentation of diarrhea?
N/V, abdo pain, HA, fever, chills, malaise, weight loss, dehydration
65
What are some prevention methods?
sanitation, hygiene - WASH HANDS!!, strict food and water handling
66
What are non-pharmacologic txs for diarrhea?
discontinue consumption of solids and diary X24 hrs (osmotic). With N/V: mild low-residue diet, as BM dec. begin bland diet. Rehydrate: oral rehydration solutions (ORS), LR, D5W, NS and maintain electrolytes.
67
How can you achieve rehydration for adults and kids?
adults: any beverage + NaCl source (salted crackers)
kids: commercial oral rehydration solutions (Pedialyte, apple juice, chicken broth, sports drinks discouraged.....hypertonic and low electrolyte concentraiton)
68
What is the proper rehydration rate?
up to 2 years: 50-100mL after each loose stool and between if possible.
2 years +: 100-200 mL after each loose stool and between is possible.
Continue extra fluid until diarrhea stops. May need IV fluids for severe dehydration
69
What are the pharmacological treatments for diarrhea?
Antimotility, Adsorbents, Antisecretory, Anticholinergic, Bacterial replacement, enzymes, antibiotics
70
What are the antimotility drugs for D?
Diphenoxylate, Loperamide, Paregoric, Difenoxin
71
What are the Adsorbent drugs for D?
Kaolin-Pectin mix, Polycarbophil, Attapulgite
72
What are the antisecretory drugs for D?
Bismuth subsalicylate
73
What are the anticholingeric drugs for D?
Atropine
74
What are the bacterial replacement drugs for D?
Lactobacillus
75
What are the enzymes for D?
Lactase
76
What are the antibiotics for D?
Metronidazole, Vancomycin
77
What are the anti-motility drugs MOA?
Slow intestinal transity, prolong contact and absorption, increase gut capacity. They are opiates and derivaties, Loperamide, Diphenoyxlate, Paregoric, Difenoxin. There is addiction potential though. And they worsen diarrhea if infectious!
78
What is Lomotil?
antimotility
Dose: adult - 2 tabs (2.5mg diphenoxylate/0.025 mg atropie per tab and per 5mL) QID or 10mL QID; kids: 0.3-0.4mg/kg up to 55kg or 12 years QID
Onset: clinical benefit w/in 48hrs, if NO benefit w/in 10 days, change therapy
79
What is the CI for Lomotil
C. diff or enterotoxin-producing bacteria
80
What is the MOA and onset for Loperamide (Imodium)? antimotility drug
MOA: acts directly on intestinal muscles to inhibit peristalsis, prolonging transit time
Onset: usually w/in 48 hrs.
(Dose: 4 mg -2 capsules- followed by 2 mg after each loose stool, max 16 mg -8 caps-/24 hrs.)
81
What are the CIs for Loperamide (Imodium)?
Patients w/fever exceeding 101F (38.3 C), acute ulcerative colitis, antibiotic associative colitic, children under 2
82
What is the MOA of Kaolin-pectin, polycarbophil, attapulgic? (the adsorbents)
absorb nutrients, toxins, drugs, and digestive juices - effectiveness is unproven, many do NOT require RX (non-toxic)
83
What is the MOA for Cholestyamine (Questran)?
| another adsorbent
absorbs bile salts and C. difficile toxin (so could ADD to abx therapy for C. diff)
84
What is the MOA for Bismuth subsalicylate?
It's pepto-bismol (an antisecretory drug)
MOA: stimulates absorption of fluid and electrolytes across the intestinal wall -- antisecretory, anti-inflammatory and antibacterial effects. NOT for kids Reye's syndrome b/c aspirin
85
What are the side effects/CIs of Bismuth subsalicylate (pepto-bismol)?
blackened stools and tongue, salicylism, can induce gout attacks in susceptible patients
Interactions: anticoags and TCN, may interfere w/radiologic studies.
86
What is the MOA, onset, etc. of Octreotide (Sandostatin)?
It's an anti-secretory drug.
MOA: blocks the release of serotonin, direct inhibitory effects -- reduces motility and facilitates water absorption from the gut
Use: official indication = control sx in pts w/metastatic vasoconstrictive intestinal peptide-secreting tumor assoc. w/D; off label: treatment of refractory D
Onset: 1-3 days, maybe 1 weeks
ADR: bradycardia, hyperglycemia
87
What is the MOA of atropine?
(anticholinergic drug)
MOA: blocks vagal tone and prolongs gut transit time
ADR: anticholinergic
CI: glauocme, BPH
88
What is the MOA of Lactobacillius
(bacterial replacement)
| MOA: restores normal flora and intestinal function -- intestinal flatus, CI in immuno-compromised pts
89
What is the MOA of Lactase enzymes?
MOA: replaces lactase enzyme def'cy -- only useful in lactose intolerance D.
90
How is Zinc used in D?
substantial data supporting Zinc as adjunct to ORS -- red. of stool output, red. of D duration. MOA unknown, possibly action on intestinal ion transport.
WHO and UNICEF rec: 20mg Zinc supplements x10-14 days for kids; 10mg per day
91
What is traveler's D?
D that develops during or w/in 10 days of travel return.
Classic: passage of 3+ unformed stools in 24 hr period plus at least 1: N/V/ab pain or cramps, fever, blood in stools
Moderate: passes of 1 or 2 unformed stools in 24 h + at least 1 of above or more than 2 unformed stools in 24 h w/o other symptoms
Mild: 1 or 2 unformed stools in 24 h w/o other symptoms
92
What are the features warranting a workup (culture)?
| b/c most treated symptomatically and initiated w/o culture
fever, colitis symptoms (bloody stools and abd cramping), stool culture should be performed (looking for Campylobacter or Shigella spp. Enterohermorrhagic E. coli and Shiga toxin).
Workup if: predominante upper GI symptoms (bloating, gas, N), examine stool for Giardia Iambila, Cyclospora and Isopora. Travel loc. should be considered. Abx for prophy then D at risk for C. diff so test also! Appear systemically ill, blood cultures for Salmonella spp.
93
What are the risks for traveler's D?
ingestion of contaminated food or drink, high risk food: undercooked veggies, unpeeled fruit, raw/undercooked mean. Risk: meals eaten at home
94
What are some prophylaxis options for traveler's d?
dietary counseling, Bismuth subsalicylate (pepto-bismol) 2 tabs or 30 mL QID; abx: effective but irresponsible; resistance is huge problem! Cipro 500 mg daily is 95% effective in some areas, but Campylobacter in Thailand is 84% resistance w/in 4 years!!
95
What is the tx for travelers D?
rehydration is key! ORS indicated. ABX: warranted in mod-severe forms, generally fluoroquinolones preferred except if travel to Asia, Cipro 500mg BID x3 days, Azithromycin 1gm x1 or 500mg daily x3 days, only if FQ or azith not available - Rifaxamin 200mg TID x3 days (should not be used if complicated by fever or blood in stool or caused by pathogen other than E. coli).
CAN use antimotilty agents but with CAUTION and ONLY w/antimicrobial therapy too.
96
What is the nosocomial diarrhea, C. diff?
pts recently hospitalized or on abx. toxin may be present for several weeks. hand washing more effective than gel.
97
What is the tx for C. diff?
Metronidazole 500mg PO Q8hrs X10-14 days (non severe)
| Vancomycin 125mg PO Q6hrs X10-14 days (severe)
98
What is IBS?
irritable bowel syndrome - most common dx in clinical gastroenterology
contributing factors: genetics, motility factors, inflammation, colonic infections, mech. irritation to local nerves, stress
Lower abdo pain, disturbed defecation and bloating w/absence of structural or biochemical explaining factors.
99
What is the presentation of IBS?
lower abdo pain, abdo bloating and distention, D symptoms >3 stools/day (extreme urgency, mucus passage), constipations symptoms
100
What is the IBS diagnostic criteria?
chronic or recurrent abdo pain >/= 6 mos. w/2 of the following: ab pain relieved by defecation, ab pain assoc. with more freq stool, ab distention, feeling of incomplete evacuation, mucus in stools
Manning Critera
Recurrent abdo pain or discomfort >/= 3 days/mo. in the last 3 mos. assoc. w/2+ of the following: relieved w/defecation, onset assoc. w/change in frequency of stool
Rome III Criteria
101
What does the AGA guideline Nov. 14 NOT look at?
dietary and lifestyle mods -- recommends meds based on EBM
102
What are the 2 types of IBS?
IBS-C (constipation) and IBS-D (diarrhea)
103
Are TCAs used for IBS tx?
yes, they are shown to have modest improvement in global relief of either type of IBS and abdo pain -- the rec. in guideline is conditional and evidence is low quality.
104
Are SSRIs used to tx IBS?
There is no improvement, so recommend AGAINST IBS tx.
105
How can you tx IBS-C?
stress mgmt and pt edu, inc. dietary fiber and fluid, pharm therapy (per guideline)
106
What is Linaclotide (Linzess)?
used to tx IBS-C
MOA: Linaclotide and active metabolite bind and agonize guanylate cyclase C on luminal surfae of intestinal epithelium resulting in subsequent chloride and bicarbonate secretion into intestinal lumen (intestinal fluid inc, GI transit dec.)
107
How benefical is Linaclotide?
In 2 RCT displayed modest beneficial effect w/both improvement in abdo pain and # of complete stools as well as improvement in global IBS sxs.
290 mcg Qday - apprvoed in ADULTS only.
ADR: diarrhea
Concern: if want to avoid D or high cost (still brand only) may choose alternative
108
Lubiprostone is used to treat what?
IBS-C; in IBS guidelines they looked at 2 RCT showing some improvement w/few ADR; approved by FDA in IBS-C for ONLY females >18. (dose = 8mcg BID). This is conditional recommendation w/moderate quality evidence. Still expensive so if cost is an issue maybe use alt.
109
What are PEG laxatives used for?
IBS-C
Very low cost and few ADR. 1 RCT didn't who any benefit but large body of evidence led to recommendation. Conditional rec. with low quality of evidence.
110
How do you tx IBS-D?
stress mgmt and pt edu, lactose and caffeine free diet as well as avoid other causative agents. Pharmacotherapy per guideline
111
What is Rifaximin used to tx?
IBS-D
inhibits bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase. Guideline recommends based on 2 RCT that showed small but beneficial improvent in abdo pain and stool consistency, another 3 RCT showed improvement in global sxs of IBS.
112
What are the ADRs and dose for Rifaximin?
ADR: peripheral edema, dizziness, fatigue - generally well tolerated.
Cheap options, conditional recommendation from modest evidence.
dose: 550mg TID x14 days, may be repeated 2 times is sxs reoccur
113
What is Alosetron?
IBS-D med. Potent 5-HT3 antagonist (blocking may reduce pain, abdo discomfot, urgency and diarrhea). ONLY FDA approved in women
ADR: constipation, dose related
dose: 0.5mg BID x4 weeks if tolerated may inc. to 1mg BID, if inadequate improvement after 4 weeks d/c
114
What is the concern with Alosteron that caused marked withdrawal?
concerns of idiopathic non dose dependent ischemic colitis. Withdrawn form market and then returned to market under physician program. Rec. in guideline as conditional rec. w/mod evidence
115
What is Lopermaide used for?
IBS-D
most trials not for IBS-D, 2 older trials show global relief however low cost, minimal ADR and large pool of evidence for D led to guideline rec. conditionally for adjunct therapy based on very low quality evidence
