User login
Bringing you the latest news, research and reviews, exclusive interviews, podcasts, quizzes, and more.
gambling
compulsive behaviors
ammunition
assault rifle
black jack
Boko Haram
bondage
child abuse
cocaine
Daech
drug paraphernalia
explosion
gun
human trafficking
ISIL
ISIS
Islamic caliphate
Islamic state
mixed martial arts
MMA
molestation
national rifle association
NRA
nsfw
pedophile
pedophilia
poker
porn
pornography
psychedelic drug
recreational drug
sex slave rings
slot machine
terrorism
terrorist
Texas hold 'em
UFC
substance abuse
abuseed
abuseer
abusees
abuseing
abusely
abuses
aeolus
aeolused
aeoluser
aeoluses
aeolusing
aeolusly
aeoluss
ahole
aholeed
aholeer
aholees
aholeing
aholely
aholes
alcohol
alcoholed
alcoholer
alcoholes
alcoholing
alcoholly
alcohols
allman
allmaned
allmaner
allmanes
allmaning
allmanly
allmans
alted
altes
alting
altly
alts
analed
analer
anales
analing
anally
analprobe
analprobeed
analprobeer
analprobees
analprobeing
analprobely
analprobes
anals
anilingus
anilingused
anilinguser
anilinguses
anilingusing
anilingusly
anilinguss
anus
anused
anuser
anuses
anusing
anusly
anuss
areola
areolaed
areolaer
areolaes
areolaing
areolaly
areolas
areole
areoleed
areoleer
areolees
areoleing
areolely
areoles
arian
arianed
arianer
arianes
arianing
arianly
arians
aryan
aryaned
aryaner
aryanes
aryaning
aryanly
aryans
asiaed
asiaer
asiaes
asiaing
asialy
asias
ass
ass hole
ass lick
ass licked
ass licker
ass lickes
ass licking
ass lickly
ass licks
assbang
assbanged
assbangeded
assbangeder
assbangedes
assbangeding
assbangedly
assbangeds
assbanger
assbanges
assbanging
assbangly
assbangs
assbangsed
assbangser
assbangses
assbangsing
assbangsly
assbangss
assed
asser
asses
assesed
asseser
asseses
assesing
assesly
assess
assfuck
assfucked
assfucker
assfuckered
assfuckerer
assfuckeres
assfuckering
assfuckerly
assfuckers
assfuckes
assfucking
assfuckly
assfucks
asshat
asshated
asshater
asshates
asshating
asshatly
asshats
assholeed
assholeer
assholees
assholeing
assholely
assholes
assholesed
assholeser
assholeses
assholesing
assholesly
assholess
assing
assly
assmaster
assmastered
assmasterer
assmasteres
assmastering
assmasterly
assmasters
assmunch
assmunched
assmuncher
assmunches
assmunching
assmunchly
assmunchs
asss
asswipe
asswipeed
asswipeer
asswipees
asswipeing
asswipely
asswipes
asswipesed
asswipeser
asswipeses
asswipesing
asswipesly
asswipess
azz
azzed
azzer
azzes
azzing
azzly
azzs
babeed
babeer
babees
babeing
babely
babes
babesed
babeser
babeses
babesing
babesly
babess
ballsac
ballsaced
ballsacer
ballsaces
ballsacing
ballsack
ballsacked
ballsacker
ballsackes
ballsacking
ballsackly
ballsacks
ballsacly
ballsacs
ballsed
ballser
ballses
ballsing
ballsly
ballss
barf
barfed
barfer
barfes
barfing
barfly
barfs
bastard
bastarded
bastarder
bastardes
bastarding
bastardly
bastards
bastardsed
bastardser
bastardses
bastardsing
bastardsly
bastardss
bawdy
bawdyed
bawdyer
bawdyes
bawdying
bawdyly
bawdys
beaner
beanered
beanerer
beaneres
beanering
beanerly
beaners
beardedclam
beardedclamed
beardedclamer
beardedclames
beardedclaming
beardedclamly
beardedclams
beastiality
beastialityed
beastialityer
beastialityes
beastialitying
beastialityly
beastialitys
beatch
beatched
beatcher
beatches
beatching
beatchly
beatchs
beater
beatered
beaterer
beateres
beatering
beaterly
beaters
beered
beerer
beeres
beering
beerly
beeyotch
beeyotched
beeyotcher
beeyotches
beeyotching
beeyotchly
beeyotchs
beotch
beotched
beotcher
beotches
beotching
beotchly
beotchs
biatch
biatched
biatcher
biatches
biatching
biatchly
biatchs
big tits
big titsed
big titser
big titses
big titsing
big titsly
big titss
bigtits
bigtitsed
bigtitser
bigtitses
bigtitsing
bigtitsly
bigtitss
bimbo
bimboed
bimboer
bimboes
bimboing
bimboly
bimbos
bisexualed
bisexualer
bisexuales
bisexualing
bisexually
bisexuals
bitch
bitched
bitcheded
bitcheder
bitchedes
bitcheding
bitchedly
bitcheds
bitcher
bitches
bitchesed
bitcheser
bitcheses
bitchesing
bitchesly
bitchess
bitching
bitchly
bitchs
bitchy
bitchyed
bitchyer
bitchyes
bitchying
bitchyly
bitchys
bleached
bleacher
bleaches
bleaching
bleachly
bleachs
blow job
blow jobed
blow jober
blow jobes
blow jobing
blow jobly
blow jobs
blowed
blower
blowes
blowing
blowjob
blowjobed
blowjober
blowjobes
blowjobing
blowjobly
blowjobs
blowjobsed
blowjobser
blowjobses
blowjobsing
blowjobsly
blowjobss
blowly
blows
boink
boinked
boinker
boinkes
boinking
boinkly
boinks
bollock
bollocked
bollocker
bollockes
bollocking
bollockly
bollocks
bollocksed
bollockser
bollockses
bollocksing
bollocksly
bollockss
bollok
bolloked
bolloker
bollokes
bolloking
bollokly
bolloks
boner
bonered
bonerer
boneres
bonering
bonerly
boners
bonersed
bonerser
bonerses
bonersing
bonersly
bonerss
bong
bonged
bonger
bonges
bonging
bongly
bongs
boob
boobed
boober
boobes
boobies
boobiesed
boobieser
boobieses
boobiesing
boobiesly
boobiess
boobing
boobly
boobs
boobsed
boobser
boobses
boobsing
boobsly
boobss
booby
boobyed
boobyer
boobyes
boobying
boobyly
boobys
booger
boogered
boogerer
boogeres
boogering
boogerly
boogers
bookie
bookieed
bookieer
bookiees
bookieing
bookiely
bookies
bootee
booteeed
booteeer
booteees
booteeing
booteely
bootees
bootie
bootieed
bootieer
bootiees
bootieing
bootiely
booties
booty
bootyed
bootyer
bootyes
bootying
bootyly
bootys
boozeed
boozeer
boozees
boozeing
boozely
boozer
boozered
boozerer
boozeres
boozering
boozerly
boozers
boozes
boozy
boozyed
boozyer
boozyes
boozying
boozyly
boozys
bosomed
bosomer
bosomes
bosoming
bosomly
bosoms
bosomy
bosomyed
bosomyer
bosomyes
bosomying
bosomyly
bosomys
bugger
buggered
buggerer
buggeres
buggering
buggerly
buggers
bukkake
bukkakeed
bukkakeer
bukkakees
bukkakeing
bukkakely
bukkakes
bull shit
bull shited
bull shiter
bull shites
bull shiting
bull shitly
bull shits
bullshit
bullshited
bullshiter
bullshites
bullshiting
bullshitly
bullshits
bullshitsed
bullshitser
bullshitses
bullshitsing
bullshitsly
bullshitss
bullshitted
bullshitteded
bullshitteder
bullshittedes
bullshitteding
bullshittedly
bullshitteds
bullturds
bullturdsed
bullturdser
bullturdses
bullturdsing
bullturdsly
bullturdss
bung
bunged
bunger
bunges
bunging
bungly
bungs
busty
bustyed
bustyer
bustyes
bustying
bustyly
bustys
butt
butt fuck
butt fucked
butt fucker
butt fuckes
butt fucking
butt fuckly
butt fucks
butted
buttes
buttfuck
buttfucked
buttfucker
buttfuckered
buttfuckerer
buttfuckeres
buttfuckering
buttfuckerly
buttfuckers
buttfuckes
buttfucking
buttfuckly
buttfucks
butting
buttly
buttplug
buttpluged
buttpluger
buttpluges
buttpluging
buttplugly
buttplugs
butts
caca
cacaed
cacaer
cacaes
cacaing
cacaly
cacas
cahone
cahoneed
cahoneer
cahonees
cahoneing
cahonely
cahones
cameltoe
cameltoeed
cameltoeer
cameltoees
cameltoeing
cameltoely
cameltoes
carpetmuncher
carpetmunchered
carpetmuncherer
carpetmuncheres
carpetmunchering
carpetmuncherly
carpetmunchers
cawk
cawked
cawker
cawkes
cawking
cawkly
cawks
chinc
chinced
chincer
chinces
chincing
chincly
chincs
chincsed
chincser
chincses
chincsing
chincsly
chincss
chink
chinked
chinker
chinkes
chinking
chinkly
chinks
chode
chodeed
chodeer
chodees
chodeing
chodely
chodes
chodesed
chodeser
chodeses
chodesing
chodesly
chodess
clit
clited
cliter
clites
cliting
clitly
clitoris
clitorised
clitoriser
clitorises
clitorising
clitorisly
clitoriss
clitorus
clitorused
clitoruser
clitoruses
clitorusing
clitorusly
clitoruss
clits
clitsed
clitser
clitses
clitsing
clitsly
clitss
clitty
clittyed
clittyer
clittyes
clittying
clittyly
clittys
cocain
cocaine
cocained
cocaineed
cocaineer
cocainees
cocaineing
cocainely
cocainer
cocaines
cocaining
cocainly
cocains
cock
cock sucker
cock suckered
cock suckerer
cock suckeres
cock suckering
cock suckerly
cock suckers
cockblock
cockblocked
cockblocker
cockblockes
cockblocking
cockblockly
cockblocks
cocked
cocker
cockes
cockholster
cockholstered
cockholsterer
cockholsteres
cockholstering
cockholsterly
cockholsters
cocking
cockknocker
cockknockered
cockknockerer
cockknockeres
cockknockering
cockknockerly
cockknockers
cockly
cocks
cocksed
cockser
cockses
cocksing
cocksly
cocksmoker
cocksmokered
cocksmokerer
cocksmokeres
cocksmokering
cocksmokerly
cocksmokers
cockss
cocksucker
cocksuckered
cocksuckerer
cocksuckeres
cocksuckering
cocksuckerly
cocksuckers
coital
coitaled
coitaler
coitales
coitaling
coitally
coitals
commie
commieed
commieer
commiees
commieing
commiely
commies
condomed
condomer
condomes
condoming
condomly
condoms
coon
cooned
cooner
coones
cooning
coonly
coons
coonsed
coonser
coonses
coonsing
coonsly
coonss
corksucker
corksuckered
corksuckerer
corksuckeres
corksuckering
corksuckerly
corksuckers
cracked
crackwhore
crackwhoreed
crackwhoreer
crackwhorees
crackwhoreing
crackwhorely
crackwhores
crap
craped
craper
crapes
craping
craply
crappy
crappyed
crappyer
crappyes
crappying
crappyly
crappys
cum
cumed
cumer
cumes
cuming
cumly
cummin
cummined
cumminer
cummines
cumming
cumminged
cumminger
cumminges
cumminging
cummingly
cummings
cummining
cumminly
cummins
cums
cumshot
cumshoted
cumshoter
cumshotes
cumshoting
cumshotly
cumshots
cumshotsed
cumshotser
cumshotses
cumshotsing
cumshotsly
cumshotss
cumslut
cumsluted
cumsluter
cumslutes
cumsluting
cumslutly
cumsluts
cumstain
cumstained
cumstainer
cumstaines
cumstaining
cumstainly
cumstains
cunilingus
cunilingused
cunilinguser
cunilinguses
cunilingusing
cunilingusly
cunilinguss
cunnilingus
cunnilingused
cunnilinguser
cunnilinguses
cunnilingusing
cunnilingusly
cunnilinguss
cunny
cunnyed
cunnyer
cunnyes
cunnying
cunnyly
cunnys
cunt
cunted
cunter
cuntes
cuntface
cuntfaceed
cuntfaceer
cuntfacees
cuntfaceing
cuntfacely
cuntfaces
cunthunter
cunthuntered
cunthunterer
cunthunteres
cunthuntering
cunthunterly
cunthunters
cunting
cuntlick
cuntlicked
cuntlicker
cuntlickered
cuntlickerer
cuntlickeres
cuntlickering
cuntlickerly
cuntlickers
cuntlickes
cuntlicking
cuntlickly
cuntlicks
cuntly
cunts
cuntsed
cuntser
cuntses
cuntsing
cuntsly
cuntss
dago
dagoed
dagoer
dagoes
dagoing
dagoly
dagos
dagosed
dagoser
dagoses
dagosing
dagosly
dagoss
dammit
dammited
dammiter
dammites
dammiting
dammitly
dammits
damn
damned
damneded
damneder
damnedes
damneding
damnedly
damneds
damner
damnes
damning
damnit
damnited
damniter
damnites
damniting
damnitly
damnits
damnly
damns
dick
dickbag
dickbaged
dickbager
dickbages
dickbaging
dickbagly
dickbags
dickdipper
dickdippered
dickdipperer
dickdipperes
dickdippering
dickdipperly
dickdippers
dicked
dicker
dickes
dickface
dickfaceed
dickfaceer
dickfacees
dickfaceing
dickfacely
dickfaces
dickflipper
dickflippered
dickflipperer
dickflipperes
dickflippering
dickflipperly
dickflippers
dickhead
dickheaded
dickheader
dickheades
dickheading
dickheadly
dickheads
dickheadsed
dickheadser
dickheadses
dickheadsing
dickheadsly
dickheadss
dicking
dickish
dickished
dickisher
dickishes
dickishing
dickishly
dickishs
dickly
dickripper
dickrippered
dickripperer
dickripperes
dickrippering
dickripperly
dickrippers
dicks
dicksipper
dicksippered
dicksipperer
dicksipperes
dicksippering
dicksipperly
dicksippers
dickweed
dickweeded
dickweeder
dickweedes
dickweeding
dickweedly
dickweeds
dickwhipper
dickwhippered
dickwhipperer
dickwhipperes
dickwhippering
dickwhipperly
dickwhippers
dickzipper
dickzippered
dickzipperer
dickzipperes
dickzippering
dickzipperly
dickzippers
diddle
diddleed
diddleer
diddlees
diddleing
diddlely
diddles
dike
dikeed
dikeer
dikees
dikeing
dikely
dikes
dildo
dildoed
dildoer
dildoes
dildoing
dildoly
dildos
dildosed
dildoser
dildoses
dildosing
dildosly
dildoss
diligaf
diligafed
diligafer
diligafes
diligafing
diligafly
diligafs
dillweed
dillweeded
dillweeder
dillweedes
dillweeding
dillweedly
dillweeds
dimwit
dimwited
dimwiter
dimwites
dimwiting
dimwitly
dimwits
dingle
dingleed
dingleer
dinglees
dingleing
dinglely
dingles
dipship
dipshiped
dipshiper
dipshipes
dipshiping
dipshiply
dipships
dizzyed
dizzyer
dizzyes
dizzying
dizzyly
dizzys
doggiestyleed
doggiestyleer
doggiestylees
doggiestyleing
doggiestylely
doggiestyles
doggystyleed
doggystyleer
doggystylees
doggystyleing
doggystylely
doggystyles
dong
donged
donger
donges
donging
dongly
dongs
doofus
doofused
doofuser
doofuses
doofusing
doofusly
doofuss
doosh
dooshed
doosher
dooshes
dooshing
dooshly
dooshs
dopeyed
dopeyer
dopeyes
dopeying
dopeyly
dopeys
douchebag
douchebaged
douchebager
douchebages
douchebaging
douchebagly
douchebags
douchebagsed
douchebagser
douchebagses
douchebagsing
douchebagsly
douchebagss
doucheed
doucheer
douchees
doucheing
douchely
douches
douchey
doucheyed
doucheyer
doucheyes
doucheying
doucheyly
doucheys
drunk
drunked
drunker
drunkes
drunking
drunkly
drunks
dumass
dumassed
dumasser
dumasses
dumassing
dumassly
dumasss
dumbass
dumbassed
dumbasser
dumbasses
dumbassesed
dumbasseser
dumbasseses
dumbassesing
dumbassesly
dumbassess
dumbassing
dumbassly
dumbasss
dummy
dummyed
dummyer
dummyes
dummying
dummyly
dummys
dyke
dykeed
dykeer
dykees
dykeing
dykely
dykes
dykesed
dykeser
dykeses
dykesing
dykesly
dykess
erotic
eroticed
eroticer
erotices
eroticing
eroticly
erotics
extacy
extacyed
extacyer
extacyes
extacying
extacyly
extacys
extasy
extasyed
extasyer
extasyes
extasying
extasyly
extasys
fack
facked
facker
fackes
facking
fackly
facks
fag
faged
fager
fages
fagg
fagged
faggeded
faggeder
faggedes
faggeding
faggedly
faggeds
fagger
fagges
fagging
faggit
faggited
faggiter
faggites
faggiting
faggitly
faggits
faggly
faggot
faggoted
faggoter
faggotes
faggoting
faggotly
faggots
faggs
faging
fagly
fagot
fagoted
fagoter
fagotes
fagoting
fagotly
fagots
fags
fagsed
fagser
fagses
fagsing
fagsly
fagss
faig
faiged
faiger
faiges
faiging
faigly
faigs
faigt
faigted
faigter
faigtes
faigting
faigtly
faigts
fannybandit
fannybandited
fannybanditer
fannybandites
fannybanditing
fannybanditly
fannybandits
farted
farter
fartes
farting
fartknocker
fartknockered
fartknockerer
fartknockeres
fartknockering
fartknockerly
fartknockers
fartly
farts
felch
felched
felcher
felchered
felcherer
felcheres
felchering
felcherly
felchers
felches
felching
felchinged
felchinger
felchinges
felchinging
felchingly
felchings
felchly
felchs
fellate
fellateed
fellateer
fellatees
fellateing
fellately
fellates
fellatio
fellatioed
fellatioer
fellatioes
fellatioing
fellatioly
fellatios
feltch
feltched
feltcher
feltchered
feltcherer
feltcheres
feltchering
feltcherly
feltchers
feltches
feltching
feltchly
feltchs
feom
feomed
feomer
feomes
feoming
feomly
feoms
fisted
fisteded
fisteder
fistedes
fisteding
fistedly
fisteds
fisting
fistinged
fistinger
fistinges
fistinging
fistingly
fistings
fisty
fistyed
fistyer
fistyes
fistying
fistyly
fistys
floozy
floozyed
floozyer
floozyes
floozying
floozyly
floozys
foad
foaded
foader
foades
foading
foadly
foads
fondleed
fondleer
fondlees
fondleing
fondlely
fondles
foobar
foobared
foobarer
foobares
foobaring
foobarly
foobars
freex
freexed
freexer
freexes
freexing
freexly
freexs
frigg
frigga
friggaed
friggaer
friggaes
friggaing
friggaly
friggas
frigged
frigger
frigges
frigging
friggly
friggs
fubar
fubared
fubarer
fubares
fubaring
fubarly
fubars
fuck
fuckass
fuckassed
fuckasser
fuckasses
fuckassing
fuckassly
fuckasss
fucked
fuckeded
fuckeder
fuckedes
fuckeding
fuckedly
fuckeds
fucker
fuckered
fuckerer
fuckeres
fuckering
fuckerly
fuckers
fuckes
fuckface
fuckfaceed
fuckfaceer
fuckfacees
fuckfaceing
fuckfacely
fuckfaces
fuckin
fuckined
fuckiner
fuckines
fucking
fuckinged
fuckinger
fuckinges
fuckinging
fuckingly
fuckings
fuckining
fuckinly
fuckins
fuckly
fucknugget
fucknuggeted
fucknuggeter
fucknuggetes
fucknuggeting
fucknuggetly
fucknuggets
fucknut
fucknuted
fucknuter
fucknutes
fucknuting
fucknutly
fucknuts
fuckoff
fuckoffed
fuckoffer
fuckoffes
fuckoffing
fuckoffly
fuckoffs
fucks
fucksed
fuckser
fuckses
fucksing
fucksly
fuckss
fucktard
fucktarded
fucktarder
fucktardes
fucktarding
fucktardly
fucktards
fuckup
fuckuped
fuckuper
fuckupes
fuckuping
fuckuply
fuckups
fuckwad
fuckwaded
fuckwader
fuckwades
fuckwading
fuckwadly
fuckwads
fuckwit
fuckwited
fuckwiter
fuckwites
fuckwiting
fuckwitly
fuckwits
fudgepacker
fudgepackered
fudgepackerer
fudgepackeres
fudgepackering
fudgepackerly
fudgepackers
fuk
fuked
fuker
fukes
fuking
fukly
fuks
fvck
fvcked
fvcker
fvckes
fvcking
fvckly
fvcks
fxck
fxcked
fxcker
fxckes
fxcking
fxckly
fxcks
gae
gaeed
gaeer
gaees
gaeing
gaely
gaes
gai
gaied
gaier
gaies
gaiing
gaily
gais
ganja
ganjaed
ganjaer
ganjaes
ganjaing
ganjaly
ganjas
gayed
gayer
gayes
gaying
gayly
gays
gaysed
gayser
gayses
gaysing
gaysly
gayss
gey
geyed
geyer
geyes
geying
geyly
geys
gfc
gfced
gfcer
gfces
gfcing
gfcly
gfcs
gfy
gfyed
gfyer
gfyes
gfying
gfyly
gfys
ghay
ghayed
ghayer
ghayes
ghaying
ghayly
ghays
ghey
gheyed
gheyer
gheyes
gheying
gheyly
gheys
gigolo
gigoloed
gigoloer
gigoloes
gigoloing
gigololy
gigolos
goatse
goatseed
goatseer
goatsees
goatseing
goatsely
goatses
godamn
godamned
godamner
godamnes
godamning
godamnit
godamnited
godamniter
godamnites
godamniting
godamnitly
godamnits
godamnly
godamns
goddam
goddamed
goddamer
goddames
goddaming
goddamly
goddammit
goddammited
goddammiter
goddammites
goddammiting
goddammitly
goddammits
goddamn
goddamned
goddamner
goddamnes
goddamning
goddamnly
goddamns
goddams
goldenshower
goldenshowered
goldenshowerer
goldenshoweres
goldenshowering
goldenshowerly
goldenshowers
gonad
gonaded
gonader
gonades
gonading
gonadly
gonads
gonadsed
gonadser
gonadses
gonadsing
gonadsly
gonadss
gook
gooked
gooker
gookes
gooking
gookly
gooks
gooksed
gookser
gookses
gooksing
gooksly
gookss
gringo
gringoed
gringoer
gringoes
gringoing
gringoly
gringos
gspot
gspoted
gspoter
gspotes
gspoting
gspotly
gspots
gtfo
gtfoed
gtfoer
gtfoes
gtfoing
gtfoly
gtfos
guido
guidoed
guidoer
guidoes
guidoing
guidoly
guidos
handjob
handjobed
handjober
handjobes
handjobing
handjobly
handjobs
hard on
hard oned
hard oner
hard ones
hard oning
hard only
hard ons
hardknight
hardknighted
hardknighter
hardknightes
hardknighting
hardknightly
hardknights
hebe
hebeed
hebeer
hebees
hebeing
hebely
hebes
heeb
heebed
heeber
heebes
heebing
heebly
heebs
hell
helled
heller
helles
helling
hellly
hells
hemp
hemped
hemper
hempes
hemping
hemply
hemps
heroined
heroiner
heroines
heroining
heroinly
heroins
herp
herped
herper
herpes
herpesed
herpeser
herpeses
herpesing
herpesly
herpess
herping
herply
herps
herpy
herpyed
herpyer
herpyes
herpying
herpyly
herpys
hitler
hitlered
hitlerer
hitleres
hitlering
hitlerly
hitlers
hived
hiver
hives
hiving
hivly
hivs
hobag
hobaged
hobager
hobages
hobaging
hobagly
hobags
homey
homeyed
homeyer
homeyes
homeying
homeyly
homeys
homo
homoed
homoer
homoes
homoey
homoeyed
homoeyer
homoeyes
homoeying
homoeyly
homoeys
homoing
homoly
homos
honky
honkyed
honkyer
honkyes
honkying
honkyly
honkys
hooch
hooched
hoocher
hooches
hooching
hoochly
hoochs
hookah
hookahed
hookaher
hookahes
hookahing
hookahly
hookahs
hooker
hookered
hookerer
hookeres
hookering
hookerly
hookers
hoor
hoored
hoorer
hoores
hooring
hoorly
hoors
hootch
hootched
hootcher
hootches
hootching
hootchly
hootchs
hooter
hootered
hooterer
hooteres
hootering
hooterly
hooters
hootersed
hooterser
hooterses
hootersing
hootersly
hooterss
horny
hornyed
hornyer
hornyes
hornying
hornyly
hornys
houstoned
houstoner
houstones
houstoning
houstonly
houstons
hump
humped
humpeded
humpeder
humpedes
humpeding
humpedly
humpeds
humper
humpes
humping
humpinged
humpinger
humpinges
humpinging
humpingly
humpings
humply
humps
husbanded
husbander
husbandes
husbanding
husbandly
husbands
hussy
hussyed
hussyer
hussyes
hussying
hussyly
hussys
hymened
hymener
hymenes
hymening
hymenly
hymens
inbred
inbreded
inbreder
inbredes
inbreding
inbredly
inbreds
incest
incested
incester
incestes
incesting
incestly
incests
injun
injuned
injuner
injunes
injuning
injunly
injuns
jackass
jackassed
jackasser
jackasses
jackassing
jackassly
jackasss
jackhole
jackholeed
jackholeer
jackholees
jackholeing
jackholely
jackholes
jackoff
jackoffed
jackoffer
jackoffes
jackoffing
jackoffly
jackoffs
jap
japed
japer
japes
japing
japly
japs
japsed
japser
japses
japsing
japsly
japss
jerkoff
jerkoffed
jerkoffer
jerkoffes
jerkoffing
jerkoffly
jerkoffs
jerks
jism
jismed
jismer
jismes
jisming
jismly
jisms
jiz
jized
jizer
jizes
jizing
jizly
jizm
jizmed
jizmer
jizmes
jizming
jizmly
jizms
jizs
jizz
jizzed
jizzeded
jizzeder
jizzedes
jizzeding
jizzedly
jizzeds
jizzer
jizzes
jizzing
jizzly
jizzs
junkie
junkieed
junkieer
junkiees
junkieing
junkiely
junkies
junky
junkyed
junkyer
junkyes
junkying
junkyly
junkys
kike
kikeed
kikeer
kikees
kikeing
kikely
kikes
kikesed
kikeser
kikeses
kikesing
kikesly
kikess
killed
killer
killes
killing
killly
kills
kinky
kinkyed
kinkyer
kinkyes
kinkying
kinkyly
kinkys
kkk
kkked
kkker
kkkes
kkking
kkkly
kkks
klan
klaned
klaner
klanes
klaning
klanly
klans
knobend
knobended
knobender
knobendes
knobending
knobendly
knobends
kooch
kooched
koocher
kooches
koochesed
koocheser
koocheses
koochesing
koochesly
koochess
kooching
koochly
koochs
kootch
kootched
kootcher
kootches
kootching
kootchly
kootchs
kraut
krauted
krauter
krautes
krauting
krautly
krauts
kyke
kykeed
kykeer
kykees
kykeing
kykely
kykes
lech
leched
lecher
leches
leching
lechly
lechs
leper
lepered
leperer
leperes
lepering
leperly
lepers
lesbiansed
lesbianser
lesbianses
lesbiansing
lesbiansly
lesbianss
lesbo
lesboed
lesboer
lesboes
lesboing
lesboly
lesbos
lesbosed
lesboser
lesboses
lesbosing
lesbosly
lesboss
lez
lezbianed
lezbianer
lezbianes
lezbianing
lezbianly
lezbians
lezbiansed
lezbianser
lezbianses
lezbiansing
lezbiansly
lezbianss
lezbo
lezboed
lezboer
lezboes
lezboing
lezboly
lezbos
lezbosed
lezboser
lezboses
lezbosing
lezbosly
lezboss
lezed
lezer
lezes
lezing
lezly
lezs
lezzie
lezzieed
lezzieer
lezziees
lezzieing
lezziely
lezzies
lezziesed
lezzieser
lezzieses
lezziesing
lezziesly
lezziess
lezzy
lezzyed
lezzyer
lezzyes
lezzying
lezzyly
lezzys
lmaoed
lmaoer
lmaoes
lmaoing
lmaoly
lmaos
lmfao
lmfaoed
lmfaoer
lmfaoes
lmfaoing
lmfaoly
lmfaos
loined
loiner
loines
loining
loinly
loins
loinsed
loinser
loinses
loinsing
loinsly
loinss
lubeed
lubeer
lubees
lubeing
lubely
lubes
lusty
lustyed
lustyer
lustyes
lustying
lustyly
lustys
massa
massaed
massaer
massaes
massaing
massaly
massas
masterbate
masterbateed
masterbateer
masterbatees
masterbateing
masterbately
masterbates
masterbating
masterbatinged
masterbatinger
masterbatinges
masterbatinging
masterbatingly
masterbatings
masterbation
masterbationed
masterbationer
masterbationes
masterbationing
masterbationly
masterbations
masturbate
masturbateed
masturbateer
masturbatees
masturbateing
masturbately
masturbates
masturbating
masturbatinged
masturbatinger
masturbatinges
masturbatinging
masturbatingly
masturbatings
masturbation
masturbationed
masturbationer
masturbationes
masturbationing
masturbationly
masturbations
methed
mether
methes
mething
methly
meths
militaryed
militaryer
militaryes
militarying
militaryly
militarys
mofo
mofoed
mofoer
mofoes
mofoing
mofoly
mofos
molest
molested
molester
molestes
molesting
molestly
molests
moolie
moolieed
moolieer
mooliees
moolieing
mooliely
moolies
moron
moroned
moroner
morones
moroning
moronly
morons
motherfucka
motherfuckaed
motherfuckaer
motherfuckaes
motherfuckaing
motherfuckaly
motherfuckas
motherfucker
motherfuckered
motherfuckerer
motherfuckeres
motherfuckering
motherfuckerly
motherfuckers
motherfucking
motherfuckinged
motherfuckinger
motherfuckinges
motherfuckinging
motherfuckingly
motherfuckings
mtherfucker
mtherfuckered
mtherfuckerer
mtherfuckeres
mtherfuckering
mtherfuckerly
mtherfuckers
mthrfucker
mthrfuckered
mthrfuckerer
mthrfuckeres
mthrfuckering
mthrfuckerly
mthrfuckers
mthrfucking
mthrfuckinged
mthrfuckinger
mthrfuckinges
mthrfuckinging
mthrfuckingly
mthrfuckings
muff
muffdiver
muffdivered
muffdiverer
muffdiveres
muffdivering
muffdiverly
muffdivers
muffed
muffer
muffes
muffing
muffly
muffs
murdered
murderer
murderes
murdering
murderly
murders
muthafuckaz
muthafuckazed
muthafuckazer
muthafuckazes
muthafuckazing
muthafuckazly
muthafuckazs
muthafucker
muthafuckered
muthafuckerer
muthafuckeres
muthafuckering
muthafuckerly
muthafuckers
mutherfucker
mutherfuckered
mutherfuckerer
mutherfuckeres
mutherfuckering
mutherfuckerly
mutherfuckers
mutherfucking
mutherfuckinged
mutherfuckinger
mutherfuckinges
mutherfuckinging
mutherfuckingly
mutherfuckings
muthrfucking
muthrfuckinged
muthrfuckinger
muthrfuckinges
muthrfuckinging
muthrfuckingly
muthrfuckings
nad
naded
nader
nades
nading
nadly
nads
nadsed
nadser
nadses
nadsing
nadsly
nadss
nakeded
nakeder
nakedes
nakeding
nakedly
nakeds
napalm
napalmed
napalmer
napalmes
napalming
napalmly
napalms
nappy
nappyed
nappyer
nappyes
nappying
nappyly
nappys
nazi
nazied
nazier
nazies
naziing
nazily
nazis
nazism
nazismed
nazismer
nazismes
nazisming
nazismly
nazisms
negro
negroed
negroer
negroes
negroing
negroly
negros
nigga
niggaed
niggaer
niggaes
niggah
niggahed
niggaher
niggahes
niggahing
niggahly
niggahs
niggaing
niggaly
niggas
niggased
niggaser
niggases
niggasing
niggasly
niggass
niggaz
niggazed
niggazer
niggazes
niggazing
niggazly
niggazs
nigger
niggered
niggerer
niggeres
niggering
niggerly
niggers
niggersed
niggerser
niggerses
niggersing
niggersly
niggerss
niggle
niggleed
niggleer
nigglees
niggleing
nigglely
niggles
niglet
nigleted
nigleter
nigletes
nigleting
nigletly
niglets
nimrod
nimroded
nimroder
nimrodes
nimroding
nimrodly
nimrods
ninny
ninnyed
ninnyer
ninnyes
ninnying
ninnyly
ninnys
nooky
nookyed
nookyer
nookyes
nookying
nookyly
nookys
nuccitelli
nuccitellied
nuccitellier
nuccitellies
nuccitelliing
nuccitellily
nuccitellis
nympho
nymphoed
nymphoer
nymphoes
nymphoing
nympholy
nymphos
opium
opiumed
opiumer
opiumes
opiuming
opiumly
opiums
orgies
orgiesed
orgieser
orgieses
orgiesing
orgiesly
orgiess
orgy
orgyed
orgyer
orgyes
orgying
orgyly
orgys
paddy
paddyed
paddyer
paddyes
paddying
paddyly
paddys
paki
pakied
pakier
pakies
pakiing
pakily
pakis
pantie
pantieed
pantieer
pantiees
pantieing
pantiely
panties
pantiesed
pantieser
pantieses
pantiesing
pantiesly
pantiess
panty
pantyed
pantyer
pantyes
pantying
pantyly
pantys
pastie
pastieed
pastieer
pastiees
pastieing
pastiely
pasties
pasty
pastyed
pastyer
pastyes
pastying
pastyly
pastys
pecker
peckered
peckerer
peckeres
peckering
peckerly
peckers
pedo
pedoed
pedoer
pedoes
pedoing
pedoly
pedophile
pedophileed
pedophileer
pedophilees
pedophileing
pedophilely
pedophiles
pedophilia
pedophiliac
pedophiliaced
pedophiliacer
pedophiliaces
pedophiliacing
pedophiliacly
pedophiliacs
pedophiliaed
pedophiliaer
pedophiliaes
pedophiliaing
pedophilialy
pedophilias
pedos
penial
penialed
penialer
peniales
penialing
penially
penials
penile
penileed
penileer
penilees
penileing
penilely
peniles
penis
penised
peniser
penises
penising
penisly
peniss
perversion
perversioned
perversioner
perversiones
perversioning
perversionly
perversions
peyote
peyoteed
peyoteer
peyotees
peyoteing
peyotely
peyotes
phuck
phucked
phucker
phuckes
phucking
phuckly
phucks
pillowbiter
pillowbitered
pillowbiterer
pillowbiteres
pillowbitering
pillowbiterly
pillowbiters
pimp
pimped
pimper
pimpes
pimping
pimply
pimps
pinko
pinkoed
pinkoer
pinkoes
pinkoing
pinkoly
pinkos
pissed
pisseded
pisseder
pissedes
pisseding
pissedly
pisseds
pisser
pisses
pissing
pissly
pissoff
pissoffed
pissoffer
pissoffes
pissoffing
pissoffly
pissoffs
pisss
polack
polacked
polacker
polackes
polacking
polackly
polacks
pollock
pollocked
pollocker
pollockes
pollocking
pollockly
pollocks
poon
pooned
pooner
poones
pooning
poonly
poons
poontang
poontanged
poontanger
poontanges
poontanging
poontangly
poontangs
porn
porned
porner
pornes
porning
pornly
porno
pornoed
pornoer
pornoes
pornography
pornographyed
pornographyer
pornographyes
pornographying
pornographyly
pornographys
pornoing
pornoly
pornos
porns
prick
pricked
pricker
prickes
pricking
prickly
pricks
prig
priged
priger
priges
priging
prigly
prigs
prostitute
prostituteed
prostituteer
prostitutees
prostituteing
prostitutely
prostitutes
prude
prudeed
prudeer
prudees
prudeing
prudely
prudes
punkass
punkassed
punkasser
punkasses
punkassing
punkassly
punkasss
punky
punkyed
punkyer
punkyes
punkying
punkyly
punkys
puss
pussed
pusser
pusses
pussies
pussiesed
pussieser
pussieses
pussiesing
pussiesly
pussiess
pussing
pussly
pusss
pussy
pussyed
pussyer
pussyes
pussying
pussyly
pussypounder
pussypoundered
pussypounderer
pussypounderes
pussypoundering
pussypounderly
pussypounders
pussys
puto
putoed
putoer
putoes
putoing
putoly
putos
queaf
queafed
queafer
queafes
queafing
queafly
queafs
queef
queefed
queefer
queefes
queefing
queefly
queefs
queer
queered
queerer
queeres
queering
queerly
queero
queeroed
queeroer
queeroes
queeroing
queeroly
queeros
queers
queersed
queerser
queerses
queersing
queersly
queerss
quicky
quickyed
quickyer
quickyes
quickying
quickyly
quickys
quim
quimed
quimer
quimes
quiming
quimly
quims
racy
racyed
racyer
racyes
racying
racyly
racys
rape
raped
rapeded
rapeder
rapedes
rapeding
rapedly
rapeds
rapeed
rapeer
rapees
rapeing
rapely
raper
rapered
raperer
raperes
rapering
raperly
rapers
rapes
rapist
rapisted
rapister
rapistes
rapisting
rapistly
rapists
raunch
raunched
rauncher
raunches
raunching
raunchly
raunchs
rectus
rectused
rectuser
rectuses
rectusing
rectusly
rectuss
reefer
reefered
reeferer
reeferes
reefering
reeferly
reefers
reetard
reetarded
reetarder
reetardes
reetarding
reetardly
reetards
reich
reiched
reicher
reiches
reiching
reichly
reichs
retard
retarded
retardeded
retardeder
retardedes
retardeding
retardedly
retardeds
retarder
retardes
retarding
retardly
retards
rimjob
rimjobed
rimjober
rimjobes
rimjobing
rimjobly
rimjobs
ritard
ritarded
ritarder
ritardes
ritarding
ritardly
ritards
rtard
rtarded
rtarder
rtardes
rtarding
rtardly
rtards
rum
rumed
rumer
rumes
ruming
rumly
rump
rumped
rumper
rumpes
rumping
rumply
rumprammer
rumprammered
rumprammerer
rumprammeres
rumprammering
rumprammerly
rumprammers
rumps
rums
ruski
ruskied
ruskier
ruskies
ruskiing
ruskily
ruskis
sadism
sadismed
sadismer
sadismes
sadisming
sadismly
sadisms
sadist
sadisted
sadister
sadistes
sadisting
sadistly
sadists
scag
scaged
scager
scages
scaging
scagly
scags
scantily
scantilyed
scantilyer
scantilyes
scantilying
scantilyly
scantilys
schlong
schlonged
schlonger
schlonges
schlonging
schlongly
schlongs
scrog
scroged
scroger
scroges
scroging
scrogly
scrogs
scrot
scrote
scroted
scroteed
scroteer
scrotees
scroteing
scrotely
scroter
scrotes
scroting
scrotly
scrots
scrotum
scrotumed
scrotumer
scrotumes
scrotuming
scrotumly
scrotums
scrud
scruded
scruder
scrudes
scruding
scrudly
scruds
scum
scumed
scumer
scumes
scuming
scumly
scums
seaman
seamaned
seamaner
seamanes
seamaning
seamanly
seamans
seamen
seamened
seamener
seamenes
seamening
seamenly
seamens
seduceed
seduceer
seducees
seduceing
seducely
seduces
semen
semened
semener
semenes
semening
semenly
semens
shamedame
shamedameed
shamedameer
shamedamees
shamedameing
shamedamely
shamedames
shit
shite
shiteater
shiteatered
shiteaterer
shiteateres
shiteatering
shiteaterly
shiteaters
shited
shiteed
shiteer
shitees
shiteing
shitely
shiter
shites
shitface
shitfaceed
shitfaceer
shitfacees
shitfaceing
shitfacely
shitfaces
shithead
shitheaded
shitheader
shitheades
shitheading
shitheadly
shitheads
shithole
shitholeed
shitholeer
shitholees
shitholeing
shitholely
shitholes
shithouse
shithouseed
shithouseer
shithousees
shithouseing
shithousely
shithouses
shiting
shitly
shits
shitsed
shitser
shitses
shitsing
shitsly
shitss
shitt
shitted
shitteded
shitteder
shittedes
shitteding
shittedly
shitteds
shitter
shittered
shitterer
shitteres
shittering
shitterly
shitters
shittes
shitting
shittly
shitts
shitty
shittyed
shittyer
shittyes
shittying
shittyly
shittys
shiz
shized
shizer
shizes
shizing
shizly
shizs
shooted
shooter
shootes
shooting
shootly
shoots
sissy
sissyed
sissyer
sissyes
sissying
sissyly
sissys
skag
skaged
skager
skages
skaging
skagly
skags
skank
skanked
skanker
skankes
skanking
skankly
skanks
slave
slaveed
slaveer
slavees
slaveing
slavely
slaves
sleaze
sleazeed
sleazeer
sleazees
sleazeing
sleazely
sleazes
sleazy
sleazyed
sleazyer
sleazyes
sleazying
sleazyly
sleazys
slut
slutdumper
slutdumpered
slutdumperer
slutdumperes
slutdumpering
slutdumperly
slutdumpers
sluted
sluter
slutes
sluting
slutkiss
slutkissed
slutkisser
slutkisses
slutkissing
slutkissly
slutkisss
slutly
sluts
slutsed
slutser
slutses
slutsing
slutsly
slutss
smegma
smegmaed
smegmaer
smegmaes
smegmaing
smegmaly
smegmas
smut
smuted
smuter
smutes
smuting
smutly
smuts
smutty
smuttyed
smuttyer
smuttyes
smuttying
smuttyly
smuttys
snatch
snatched
snatcher
snatches
snatching
snatchly
snatchs
sniper
snipered
sniperer
sniperes
snipering
sniperly
snipers
snort
snorted
snorter
snortes
snorting
snortly
snorts
snuff
snuffed
snuffer
snuffes
snuffing
snuffly
snuffs
sodom
sodomed
sodomer
sodomes
sodoming
sodomly
sodoms
spic
spiced
spicer
spices
spicing
spick
spicked
spicker
spickes
spicking
spickly
spicks
spicly
spics
spik
spoof
spoofed
spoofer
spoofes
spoofing
spoofly
spoofs
spooge
spoogeed
spoogeer
spoogees
spoogeing
spoogely
spooges
spunk
spunked
spunker
spunkes
spunking
spunkly
spunks
steamyed
steamyer
steamyes
steamying
steamyly
steamys
stfu
stfued
stfuer
stfues
stfuing
stfuly
stfus
stiffy
stiffyed
stiffyer
stiffyes
stiffying
stiffyly
stiffys
stoneded
stoneder
stonedes
stoneding
stonedly
stoneds
stupided
stupider
stupides
stupiding
stupidly
stupids
suckeded
suckeder
suckedes
suckeding
suckedly
suckeds
sucker
suckes
sucking
suckinged
suckinger
suckinges
suckinging
suckingly
suckings
suckly
sucks
sumofabiatch
sumofabiatched
sumofabiatcher
sumofabiatches
sumofabiatching
sumofabiatchly
sumofabiatchs
tard
tarded
tarder
tardes
tarding
tardly
tards
tawdry
tawdryed
tawdryer
tawdryes
tawdrying
tawdryly
tawdrys
teabagging
teabagginged
teabagginger
teabagginges
teabagginging
teabaggingly
teabaggings
terd
terded
terder
terdes
terding
terdly
terds
teste
testee
testeed
testeeed
testeeer
testeees
testeeing
testeely
testeer
testees
testeing
testely
testes
testesed
testeser
testeses
testesing
testesly
testess
testicle
testicleed
testicleer
testiclees
testicleing
testiclely
testicles
testis
testised
testiser
testises
testising
testisly
testiss
thrusted
thruster
thrustes
thrusting
thrustly
thrusts
thug
thuged
thuger
thuges
thuging
thugly
thugs
tinkle
tinkleed
tinkleer
tinklees
tinkleing
tinklely
tinkles
tit
tited
titer
tites
titfuck
titfucked
titfucker
titfuckes
titfucking
titfuckly
titfucks
titi
titied
titier
tities
titiing
titily
titing
titis
titly
tits
titsed
titser
titses
titsing
titsly
titss
tittiefucker
tittiefuckered
tittiefuckerer
tittiefuckeres
tittiefuckering
tittiefuckerly
tittiefuckers
titties
tittiesed
tittieser
tittieses
tittiesing
tittiesly
tittiess
titty
tittyed
tittyer
tittyes
tittyfuck
tittyfucked
tittyfucker
tittyfuckered
tittyfuckerer
tittyfuckeres
tittyfuckering
tittyfuckerly
tittyfuckers
tittyfuckes
tittyfucking
tittyfuckly
tittyfucks
tittying
tittyly
tittys
toke
tokeed
tokeer
tokees
tokeing
tokely
tokes
toots
tootsed
tootser
tootses
tootsing
tootsly
tootss
tramp
tramped
tramper
trampes
tramping
tramply
tramps
transsexualed
transsexualer
transsexuales
transsexualing
transsexually
transsexuals
trashy
trashyed
trashyer
trashyes
trashying
trashyly
trashys
tubgirl
tubgirled
tubgirler
tubgirles
tubgirling
tubgirlly
tubgirls
turd
turded
turder
turdes
turding
turdly
turds
tush
tushed
tusher
tushes
tushing
tushly
tushs
twat
twated
twater
twates
twating
twatly
twats
twatsed
twatser
twatses
twatsing
twatsly
twatss
undies
undiesed
undieser
undieses
undiesing
undiesly
undiess
unweded
unweder
unwedes
unweding
unwedly
unweds
uzi
uzied
uzier
uzies
uziing
uzily
uzis
vag
vaged
vager
vages
vaging
vagly
vags
valium
valiumed
valiumer
valiumes
valiuming
valiumly
valiums
venous
virgined
virginer
virgines
virgining
virginly
virgins
vixen
vixened
vixener
vixenes
vixening
vixenly
vixens
vodkaed
vodkaer
vodkaes
vodkaing
vodkaly
vodkas
voyeur
voyeured
voyeurer
voyeures
voyeuring
voyeurly
voyeurs
vulgar
vulgared
vulgarer
vulgares
vulgaring
vulgarly
vulgars
wang
wanged
wanger
wanges
wanging
wangly
wangs
wank
wanked
wanker
wankered
wankerer
wankeres
wankering
wankerly
wankers
wankes
wanking
wankly
wanks
wazoo
wazooed
wazooer
wazooes
wazooing
wazooly
wazoos
wedgie
wedgieed
wedgieer
wedgiees
wedgieing
wedgiely
wedgies
weeded
weeder
weedes
weeding
weedly
weeds
weenie
weenieed
weenieer
weeniees
weenieing
weeniely
weenies
weewee
weeweeed
weeweeer
weeweees
weeweeing
weeweely
weewees
weiner
weinered
weinerer
weineres
weinering
weinerly
weiners
weirdo
weirdoed
weirdoer
weirdoes
weirdoing
weirdoly
weirdos
wench
wenched
wencher
wenches
wenching
wenchly
wenchs
wetback
wetbacked
wetbacker
wetbackes
wetbacking
wetbackly
wetbacks
whitey
whiteyed
whiteyer
whiteyes
whiteying
whiteyly
whiteys
whiz
whized
whizer
whizes
whizing
whizly
whizs
whoralicious
whoralicioused
whoraliciouser
whoraliciouses
whoraliciousing
whoraliciously
whoraliciouss
whore
whorealicious
whorealicioused
whorealiciouser
whorealiciouses
whorealiciousing
whorealiciously
whorealiciouss
whored
whoreded
whoreder
whoredes
whoreding
whoredly
whoreds
whoreed
whoreer
whorees
whoreface
whorefaceed
whorefaceer
whorefacees
whorefaceing
whorefacely
whorefaces
whorehopper
whorehoppered
whorehopperer
whorehopperes
whorehoppering
whorehopperly
whorehoppers
whorehouse
whorehouseed
whorehouseer
whorehousees
whorehouseing
whorehousely
whorehouses
whoreing
whorely
whores
whoresed
whoreser
whoreses
whoresing
whoresly
whoress
whoring
whoringed
whoringer
whoringes
whoringing
whoringly
whorings
wigger
wiggered
wiggerer
wiggeres
wiggering
wiggerly
wiggers
woody
woodyed
woodyer
woodyes
woodying
woodyly
woodys
wop
woped
woper
wopes
woping
woply
wops
wtf
wtfed
wtfer
wtfes
wtfing
wtfly
wtfs
xxx
xxxed
xxxer
xxxes
xxxing
xxxly
xxxs
yeasty
yeastyed
yeastyer
yeastyes
yeastying
yeastyly
yeastys
yobbo
yobboed
yobboer
yobboes
yobboing
yobboly
yobbos
zoophile
zoophileed
zoophileer
zoophilees
zoophileing
zoophilely
zoophiles
anal
ass
ass lick
balls
ballsac
bisexual
bleach
causas
cheap
cost of miracles
cunt
display network stats
fart
fda and death
fda AND warn
fda AND warning
fda AND warns
feom
fuck
gfc
humira AND expensive
illegal
madvocate
masturbation
nuccitelli
overdose
porn
shit
snort
texarkana
Bipolar depression
Depression
adolescent depression
adolescent major depressive disorder
adolescent schizophrenia
adolescent with major depressive disorder
animals
autism
baby
brexpiprazole
child
child bipolar
child depression
child schizophrenia
children with bipolar disorder
children with depression
children with major depressive disorder
compulsive behaviors
cure
elderly bipolar
elderly depression
elderly major depressive disorder
elderly schizophrenia
elderly with dementia
first break
first episode
gambling
gaming
geriatric depression
geriatric major depressive disorder
geriatric schizophrenia
infant
kid
major depressive disorder
major depressive disorder in adolescents
major depressive disorder in children
parenting
pediatric
pediatric bipolar
pediatric depression
pediatric major depressive disorder
pediatric schizophrenia
pregnancy
pregnant
rexulti
skin care
teen
wine
section[contains(@class, 'nav-hidden')]
footer[@id='footer']
div[contains(@class, 'pane-node-field-article-topics')]
section[contains(@class, 'footer-nav-section-wrapper')]
section[contains(@class, 'content-row')]
div[contains(@class, 'panel-pane pane-article-read-next')]
A peer-reviewed clinical journal serving healthcare professionals working with the Department of Veterans Affairs, the Department of Defense, and the Public Health Service.
COVID-19: Problematic gambling could worsen
The confluence of isolation, excess available time, and anxiety about illness or finances as a result of the COVID-19 pandemic have the potential to increase problem gambling behaviors during this public health emergency, so it’s essential to gather data and supply guidance on this issue, according to a call to action published May 18 in the Journal of Addiction Medicine.
“When facing an unforeseen situation with confinement, fear of disease, and financial uncertainty for the future, problem gambling may be an important health hazard to monitor and prevent during and following the COVID-19 crisis, especially given current online gambling availability,” wrote Anders Håkansson, PhD, of Lund University in Sweden and coauthors.
Both stress and trauma have been linked to gambling problems, and both are occurring during the pandemic, said coauthor Marc N. Potenza, MD, PhD, of Yale University, New Haven, Conn., in an interview.
“People are likely to be experiencing stress at levels they haven’t experienced previously,” Dr. Potenza said. While multiple factors can contribute to addictive behaviors, “with respect to the pandemic, one concern is that so-called negative reinforcement motivations – engaging in an addictive behavior to escape from depressed or negative mood states – may be a driving motivation for a significant number of people during this time,” he said.
David Hodgins, PhD, CPsych, a professor of psychology at the University of Calgary in Alberta, who was not involved with the commentary, noted that gambling relapse is triggered by “negative emotional states, interpersonal stress, and financial stress” – all three of which the pandemic contributes to.
Financial stress can especially “inflame erroneous gambling-related cognitions,” he said in an interview, including “beliefs such as the idea that gambling can solve financial problems, even when this is statistically almost impossible as debt increases, and that debt has been caused by gambling.”
Increased social isolation also is particularly problematic, pointed out Shane W. Kraus, PhD, from the University of Nevada, Las Vegas. Dr. Kraus also was not involved with the paper.
“If someone is already struggling with already negative emotions, negative feelings, thoughts, and depression, and you’re now isolating them quite a bit, that’s not going to be a recipe for success,” Dr. Kraus said in an interview.
Dr. Potenza said.
“We should be mindful of ways in which people develop addictions in these settings,” he said. “One of the aspects of the pandemic is that many people are at home for longer periods of time, and they use digital technologies more frequently.”
The use of digital technologies can include interaction on social media platforms and on meeting applications such as Zoom, but such use also offers opportunities for problematic gambling, gaming, and pornography use. The World Health Organization recognizes addiction disorders for gambling and for gaming, and online gaming platforms and pornography sites have reported substantial increases in their traffic during the pandemic, Dr. Potenza said.
The increase in frequency is unsurprising and not necessarily a concern by itself, Dr. Kraus said.
“It’s all about loss of control or difficulty engaging or disengaging,” Dr. Kraus said. “When you can’t stop doing something even if you like it or love it, when it interferes with your day-to-day activities and relationships, that’s when it’s a problem.”
Gambling online: Easy, available
The authors note that past research has identified increased gambling problems during economic crises in other countries.
“While currently speculative, financial hardships may promote gambling as individuals may be motivated to gamble to try to win money,” the authors suggested. “Although presently limited, existing data suggest that COVID-19–related financial concerns may increase gambling-related harms, and this possibility merits systematic research.”
But trends and characteristics of the gambling market, including direct effects from the pandemic, can potentially influence behaviors, too. Most casinos have closed during the pandemic, and most of the sports that people bet on have been canceled or postponed.
“Fewer people are gambling on sports, but they turn then to other areas,” Dr. Potenza said. “If they can’t bet on major league type sports, they might gamble on more local sporting events, or they may bet on other activities going on in society during the pandemic.”
But online gambling poses greater risk.
“Properties of online gambling may constitute a particular health hazard when many people are confined to their homes and have had rapid changes in working conditions, psychosocial stress, anxiety, and depression, as has been described in China,” the paper’s authors wrote. “Online gambling may be particularly concerning due to its availability and velocity” and association with higher debt levels.
In addition to online gaming’s ease and availability, past research has found patients report boredom and escapism as reasons they turned to it.
Again, boredom on its own is not necessarily a problem, but for those who already struggle with addictive behaviors, it can be a trigger, Dr. Kraus said.
“Boredom is very tough for them because it’s often associated with negative emotions,” such as dwelling on things not going well in their lives, he said. “In a pandemic, people are by themselves quite a bit, socially isolated, so for those who are struggling already with some depression or anxiety, it’s only going to be increased.”
Online gaming trends may vary with demographics, however. Dr. Kraus noted that his former clinic at the Veterans Administration has been seeing lower gambling in patients with addictive disorders, but those patients are also older and primarily frequented casinos.
“It’s going to depend on age and familiarity with technology,” he said, but even if older problem gamblers are not going to the Internet now, “let’s wait and see what happens in the next 2 or 3 months.”
The authors noted results from a small survey of patients in treatment for gambling addiction at the Bellvitge University Hospital in Barcelona, Spain, where two of the coauthors work. They conducted telephone surveys with 26 patients about the first 4 weeks of sheltering in place because of the coronavirus. All but four of the patients were male, and their average age was 45 years.
“Most presented worries about increased uncertainties, such as the negative impact on their work, risk of COVID-19 infection of themselves or their loved ones and their treatment,” the authors reported.
Although 19% were completely abstinent, an additional 12% (n = 3) reported worsened gambling. In addition, almost half (46%) reported anxiety symptoms and more than a quarter (27%) had depressive symptoms.
Appropriate care
A particularly complicating factor of the pandemic is how it has disrupted traditional ways of seeking health care, particularly with how much mental health and other medical care has shifted to telehealth and online delivery, Dr. Potenza pointed out.
“This is a change for many people, and it’s important for both caretakers and people in treatment to be mindful of this and to try to ensure that appropriate services are maintained for people during this time,” he said.
For example, 12-step programs traditionally meet in person, which is largely impossible during the pandemic. Some have moved meetings online, and other programs have turned to apps, such as the Addiction Policy Forum’s app Connections, an empirically validated digital therapy platform that lets patients and clinicians remain connected with remote check-ins.
The move to more telehealth may actually increase access, suggested Dr. Hodgins.
“There is no evidence that this is less effective, and in fact, its convenience might be an advantage in reaching more people,” he said. “More challenging is offering group therapies remotely, but this is also feasible.”
The treatment with the strongest evidence remains cognitive-behavioral therapy (CBT), Dr. Hodgins said.
“This therapy, in part, helps people become aware of their erroneous cognitions and to challenge them, but also helps people restructure their activities to change their habits,” he said. He also noted the rise of online therapy, whether supported by a therapist or entirely self-directed, such as Gambling Self-help.
“These programs typically provide cognitive behavior content but also content that comes from studying how people recover from gambling problems,” he said. “The challenge of completely self-directed approaches is follow-through. Like most online content, people tend to flit around more than they might in therapy.” Still, he added, research has shown good outcomes from these programs.
Dr. Potenza also noted that several organizations, including the International Society of Addiction Medicine and Children and Screens, have been hosting webinars related to COVID-19 coping and/or addiction that clinicians and patients might find helpful.
Identification of problematic behaviors
One challenge in watching for problematic gambling behaviors during the pandemic is the set of unusual living circumstances for most people right now. At almost no other time in history have people been primarily confined to their homes, many unable to go to work or working from home, with extra leisure time and nowhere to go.
“With the COVID-19 pandemic, a lot of daily life has changed,” Dr. Potenza said. “It’s unclear whether certain behaviors that have become habitual during the pandemic, such as gaming or online gambling, will then interfere with daily life when the pandemic subsides.”
“The problem is, a small proportion of people who are very vulnerable will develop a disorder and might maintain it,” Dr. Kraus said. Those who already struggle with mental health and may be out of work have greater potential for problematic behaviors.
Dr. Potenza collaborated with other psychiatrists in drafting consensus guidelines on maintaining healthy use of the Internet specifically during the pandemic (Compr Psychiatry. 2020 Jul. doi: 10.10161/comppsych.2020.152180).
“It’s important to think about where one draws the line between normative everyday behaviors – behaviors that are not interfering with life functioning – and those that do interfere with life functioning,” Dr. Potenza said. “If someone is having difficulty making work or family or school obligations, these are important signs that the behavior may be problematic.”
He offered suggestions for things people can do to promote their health during the pandemic, such as having regular routines that include getting physical exercise and social interaction, dining with family if isolating together, and making time for self-care. He also recommended setting limits on the use of digital devices and aiming for a healthy balance in keeping up with the news. The idea is to stay aware of what’s happening without getting burned out or traumatized by news coverage.
Guidance for clinicians
An urgent need for research and guidelines related to gambling and the pandemic exists, the authors argued.
In the meantime, aside from various validated screeners available, Dr. Kraus offered some practical advice for clinicians checking in with their patients: “Ask your patients what they have been doing to cope with this difficult time.”
Some might mention their faith, family, or friends, and others might not have an answer or mention drinking, gaming, or engaging in other activities. “We all do things to cope. Sometimes you use healthy coping and sometimes you use unhealthy coping,” Dr. Kraus said. “I would have a dialogue with my patients around, ‘How are you getting through? What’s helping you? What are some things you’ve tried that are tripping you up?’ ”
If gambling in particular is a possible concern, he encouraged clinicians to ask their patients whether they have tried to quit or what would happen if they stopped gambling.
“What we’d expect is the problem gamblers will have more irritability, crankiness, difficulty with quitting,” he said.
Dr. Hodgins agreed that checking in on how patients’ lives and activities have changed, and their emotion reactions to those changes, is prudent.
“The change in activities might be healthy or might include increased addictive behaviors, including increased use of substances, gaming, pornography, food, and gambling,” he said.
In addition, the paper authors list several examples of guidelines that might be considered in drafting guidance for clinicians, including the following:
- Limiting the extent of gambling
- Not gambling to regulate negative emotions
- Not gambling in order to try to solve financial problems or financial concerns
- Not gambling under the influence of alcohol or drugs
- Carefully monitoring gambling-related time and financial expenditures
- Maintaining and establishing daily routines involving activities other than gambling
- Minding gambling-related attitudes and behaviors in the presence of minors
- Not starting to gamble because of stressors
The research did not receive external funding. Dr. Håkansson has received research funding from the Swedish Sport Foundation, the Swedish alcohol monopoly Systembolaget, and the Swedish state-owned gambling operator AB Svenska Spel. He is working with the company Kontigo Care on devices for gambling addiction follow-up care. Dr. Potenza has received consulting or advisory compensation from several entities, including the Addiction Policy Forum, AXA Gaming, Idorsia, Opiant, and RiverMend Health. Dr. Potenza has received research funding from Mohegan Sun casino and the National Center for Responsible Gaming. No other authors or outside sources had industry-related disclosures.
SOURCE: Håkansson A et al. J Addict Med. 2020 May 18. doi: 10.1097/ADM.0000000000000690.
The confluence of isolation, excess available time, and anxiety about illness or finances as a result of the COVID-19 pandemic have the potential to increase problem gambling behaviors during this public health emergency, so it’s essential to gather data and supply guidance on this issue, according to a call to action published May 18 in the Journal of Addiction Medicine.
“When facing an unforeseen situation with confinement, fear of disease, and financial uncertainty for the future, problem gambling may be an important health hazard to monitor and prevent during and following the COVID-19 crisis, especially given current online gambling availability,” wrote Anders Håkansson, PhD, of Lund University in Sweden and coauthors.
Both stress and trauma have been linked to gambling problems, and both are occurring during the pandemic, said coauthor Marc N. Potenza, MD, PhD, of Yale University, New Haven, Conn., in an interview.
“People are likely to be experiencing stress at levels they haven’t experienced previously,” Dr. Potenza said. While multiple factors can contribute to addictive behaviors, “with respect to the pandemic, one concern is that so-called negative reinforcement motivations – engaging in an addictive behavior to escape from depressed or negative mood states – may be a driving motivation for a significant number of people during this time,” he said.
David Hodgins, PhD, CPsych, a professor of psychology at the University of Calgary in Alberta, who was not involved with the commentary, noted that gambling relapse is triggered by “negative emotional states, interpersonal stress, and financial stress” – all three of which the pandemic contributes to.
Financial stress can especially “inflame erroneous gambling-related cognitions,” he said in an interview, including “beliefs such as the idea that gambling can solve financial problems, even when this is statistically almost impossible as debt increases, and that debt has been caused by gambling.”
Increased social isolation also is particularly problematic, pointed out Shane W. Kraus, PhD, from the University of Nevada, Las Vegas. Dr. Kraus also was not involved with the paper.
“If someone is already struggling with already negative emotions, negative feelings, thoughts, and depression, and you’re now isolating them quite a bit, that’s not going to be a recipe for success,” Dr. Kraus said in an interview.
Dr. Potenza said.
“We should be mindful of ways in which people develop addictions in these settings,” he said. “One of the aspects of the pandemic is that many people are at home for longer periods of time, and they use digital technologies more frequently.”
The use of digital technologies can include interaction on social media platforms and on meeting applications such as Zoom, but such use also offers opportunities for problematic gambling, gaming, and pornography use. The World Health Organization recognizes addiction disorders for gambling and for gaming, and online gaming platforms and pornography sites have reported substantial increases in their traffic during the pandemic, Dr. Potenza said.
The increase in frequency is unsurprising and not necessarily a concern by itself, Dr. Kraus said.
“It’s all about loss of control or difficulty engaging or disengaging,” Dr. Kraus said. “When you can’t stop doing something even if you like it or love it, when it interferes with your day-to-day activities and relationships, that’s when it’s a problem.”
Gambling online: Easy, available
The authors note that past research has identified increased gambling problems during economic crises in other countries.
“While currently speculative, financial hardships may promote gambling as individuals may be motivated to gamble to try to win money,” the authors suggested. “Although presently limited, existing data suggest that COVID-19–related financial concerns may increase gambling-related harms, and this possibility merits systematic research.”
But trends and characteristics of the gambling market, including direct effects from the pandemic, can potentially influence behaviors, too. Most casinos have closed during the pandemic, and most of the sports that people bet on have been canceled or postponed.
“Fewer people are gambling on sports, but they turn then to other areas,” Dr. Potenza said. “If they can’t bet on major league type sports, they might gamble on more local sporting events, or they may bet on other activities going on in society during the pandemic.”
But online gambling poses greater risk.
“Properties of online gambling may constitute a particular health hazard when many people are confined to their homes and have had rapid changes in working conditions, psychosocial stress, anxiety, and depression, as has been described in China,” the paper’s authors wrote. “Online gambling may be particularly concerning due to its availability and velocity” and association with higher debt levels.
In addition to online gaming’s ease and availability, past research has found patients report boredom and escapism as reasons they turned to it.
Again, boredom on its own is not necessarily a problem, but for those who already struggle with addictive behaviors, it can be a trigger, Dr. Kraus said.
“Boredom is very tough for them because it’s often associated with negative emotions,” such as dwelling on things not going well in their lives, he said. “In a pandemic, people are by themselves quite a bit, socially isolated, so for those who are struggling already with some depression or anxiety, it’s only going to be increased.”
Online gaming trends may vary with demographics, however. Dr. Kraus noted that his former clinic at the Veterans Administration has been seeing lower gambling in patients with addictive disorders, but those patients are also older and primarily frequented casinos.
“It’s going to depend on age and familiarity with technology,” he said, but even if older problem gamblers are not going to the Internet now, “let’s wait and see what happens in the next 2 or 3 months.”
The authors noted results from a small survey of patients in treatment for gambling addiction at the Bellvitge University Hospital in Barcelona, Spain, where two of the coauthors work. They conducted telephone surveys with 26 patients about the first 4 weeks of sheltering in place because of the coronavirus. All but four of the patients were male, and their average age was 45 years.
“Most presented worries about increased uncertainties, such as the negative impact on their work, risk of COVID-19 infection of themselves or their loved ones and their treatment,” the authors reported.
Although 19% were completely abstinent, an additional 12% (n = 3) reported worsened gambling. In addition, almost half (46%) reported anxiety symptoms and more than a quarter (27%) had depressive symptoms.
Appropriate care
A particularly complicating factor of the pandemic is how it has disrupted traditional ways of seeking health care, particularly with how much mental health and other medical care has shifted to telehealth and online delivery, Dr. Potenza pointed out.
“This is a change for many people, and it’s important for both caretakers and people in treatment to be mindful of this and to try to ensure that appropriate services are maintained for people during this time,” he said.
For example, 12-step programs traditionally meet in person, which is largely impossible during the pandemic. Some have moved meetings online, and other programs have turned to apps, such as the Addiction Policy Forum’s app Connections, an empirically validated digital therapy platform that lets patients and clinicians remain connected with remote check-ins.
The move to more telehealth may actually increase access, suggested Dr. Hodgins.
“There is no evidence that this is less effective, and in fact, its convenience might be an advantage in reaching more people,” he said. “More challenging is offering group therapies remotely, but this is also feasible.”
The treatment with the strongest evidence remains cognitive-behavioral therapy (CBT), Dr. Hodgins said.
“This therapy, in part, helps people become aware of their erroneous cognitions and to challenge them, but also helps people restructure their activities to change their habits,” he said. He also noted the rise of online therapy, whether supported by a therapist or entirely self-directed, such as Gambling Self-help.
“These programs typically provide cognitive behavior content but also content that comes from studying how people recover from gambling problems,” he said. “The challenge of completely self-directed approaches is follow-through. Like most online content, people tend to flit around more than they might in therapy.” Still, he added, research has shown good outcomes from these programs.
Dr. Potenza also noted that several organizations, including the International Society of Addiction Medicine and Children and Screens, have been hosting webinars related to COVID-19 coping and/or addiction that clinicians and patients might find helpful.
Identification of problematic behaviors
One challenge in watching for problematic gambling behaviors during the pandemic is the set of unusual living circumstances for most people right now. At almost no other time in history have people been primarily confined to their homes, many unable to go to work or working from home, with extra leisure time and nowhere to go.
“With the COVID-19 pandemic, a lot of daily life has changed,” Dr. Potenza said. “It’s unclear whether certain behaviors that have become habitual during the pandemic, such as gaming or online gambling, will then interfere with daily life when the pandemic subsides.”
“The problem is, a small proportion of people who are very vulnerable will develop a disorder and might maintain it,” Dr. Kraus said. Those who already struggle with mental health and may be out of work have greater potential for problematic behaviors.
Dr. Potenza collaborated with other psychiatrists in drafting consensus guidelines on maintaining healthy use of the Internet specifically during the pandemic (Compr Psychiatry. 2020 Jul. doi: 10.10161/comppsych.2020.152180).
“It’s important to think about where one draws the line between normative everyday behaviors – behaviors that are not interfering with life functioning – and those that do interfere with life functioning,” Dr. Potenza said. “If someone is having difficulty making work or family or school obligations, these are important signs that the behavior may be problematic.”
He offered suggestions for things people can do to promote their health during the pandemic, such as having regular routines that include getting physical exercise and social interaction, dining with family if isolating together, and making time for self-care. He also recommended setting limits on the use of digital devices and aiming for a healthy balance in keeping up with the news. The idea is to stay aware of what’s happening without getting burned out or traumatized by news coverage.
Guidance for clinicians
An urgent need for research and guidelines related to gambling and the pandemic exists, the authors argued.
In the meantime, aside from various validated screeners available, Dr. Kraus offered some practical advice for clinicians checking in with their patients: “Ask your patients what they have been doing to cope with this difficult time.”
Some might mention their faith, family, or friends, and others might not have an answer or mention drinking, gaming, or engaging in other activities. “We all do things to cope. Sometimes you use healthy coping and sometimes you use unhealthy coping,” Dr. Kraus said. “I would have a dialogue with my patients around, ‘How are you getting through? What’s helping you? What are some things you’ve tried that are tripping you up?’ ”
If gambling in particular is a possible concern, he encouraged clinicians to ask their patients whether they have tried to quit or what would happen if they stopped gambling.
“What we’d expect is the problem gamblers will have more irritability, crankiness, difficulty with quitting,” he said.
Dr. Hodgins agreed that checking in on how patients’ lives and activities have changed, and their emotion reactions to those changes, is prudent.
“The change in activities might be healthy or might include increased addictive behaviors, including increased use of substances, gaming, pornography, food, and gambling,” he said.
In addition, the paper authors list several examples of guidelines that might be considered in drafting guidance for clinicians, including the following:
- Limiting the extent of gambling
- Not gambling to regulate negative emotions
- Not gambling in order to try to solve financial problems or financial concerns
- Not gambling under the influence of alcohol or drugs
- Carefully monitoring gambling-related time and financial expenditures
- Maintaining and establishing daily routines involving activities other than gambling
- Minding gambling-related attitudes and behaviors in the presence of minors
- Not starting to gamble because of stressors
The research did not receive external funding. Dr. Håkansson has received research funding from the Swedish Sport Foundation, the Swedish alcohol monopoly Systembolaget, and the Swedish state-owned gambling operator AB Svenska Spel. He is working with the company Kontigo Care on devices for gambling addiction follow-up care. Dr. Potenza has received consulting or advisory compensation from several entities, including the Addiction Policy Forum, AXA Gaming, Idorsia, Opiant, and RiverMend Health. Dr. Potenza has received research funding from Mohegan Sun casino and the National Center for Responsible Gaming. No other authors or outside sources had industry-related disclosures.
SOURCE: Håkansson A et al. J Addict Med. 2020 May 18. doi: 10.1097/ADM.0000000000000690.
The confluence of isolation, excess available time, and anxiety about illness or finances as a result of the COVID-19 pandemic have the potential to increase problem gambling behaviors during this public health emergency, so it’s essential to gather data and supply guidance on this issue, according to a call to action published May 18 in the Journal of Addiction Medicine.
“When facing an unforeseen situation with confinement, fear of disease, and financial uncertainty for the future, problem gambling may be an important health hazard to monitor and prevent during and following the COVID-19 crisis, especially given current online gambling availability,” wrote Anders Håkansson, PhD, of Lund University in Sweden and coauthors.
Both stress and trauma have been linked to gambling problems, and both are occurring during the pandemic, said coauthor Marc N. Potenza, MD, PhD, of Yale University, New Haven, Conn., in an interview.
“People are likely to be experiencing stress at levels they haven’t experienced previously,” Dr. Potenza said. While multiple factors can contribute to addictive behaviors, “with respect to the pandemic, one concern is that so-called negative reinforcement motivations – engaging in an addictive behavior to escape from depressed or negative mood states – may be a driving motivation for a significant number of people during this time,” he said.
David Hodgins, PhD, CPsych, a professor of psychology at the University of Calgary in Alberta, who was not involved with the commentary, noted that gambling relapse is triggered by “negative emotional states, interpersonal stress, and financial stress” – all three of which the pandemic contributes to.
Financial stress can especially “inflame erroneous gambling-related cognitions,” he said in an interview, including “beliefs such as the idea that gambling can solve financial problems, even when this is statistically almost impossible as debt increases, and that debt has been caused by gambling.”
Increased social isolation also is particularly problematic, pointed out Shane W. Kraus, PhD, from the University of Nevada, Las Vegas. Dr. Kraus also was not involved with the paper.
“If someone is already struggling with already negative emotions, negative feelings, thoughts, and depression, and you’re now isolating them quite a bit, that’s not going to be a recipe for success,” Dr. Kraus said in an interview.
Dr. Potenza said.
“We should be mindful of ways in which people develop addictions in these settings,” he said. “One of the aspects of the pandemic is that many people are at home for longer periods of time, and they use digital technologies more frequently.”
The use of digital technologies can include interaction on social media platforms and on meeting applications such as Zoom, but such use also offers opportunities for problematic gambling, gaming, and pornography use. The World Health Organization recognizes addiction disorders for gambling and for gaming, and online gaming platforms and pornography sites have reported substantial increases in their traffic during the pandemic, Dr. Potenza said.
The increase in frequency is unsurprising and not necessarily a concern by itself, Dr. Kraus said.
“It’s all about loss of control or difficulty engaging or disengaging,” Dr. Kraus said. “When you can’t stop doing something even if you like it or love it, when it interferes with your day-to-day activities and relationships, that’s when it’s a problem.”
Gambling online: Easy, available
The authors note that past research has identified increased gambling problems during economic crises in other countries.
“While currently speculative, financial hardships may promote gambling as individuals may be motivated to gamble to try to win money,” the authors suggested. “Although presently limited, existing data suggest that COVID-19–related financial concerns may increase gambling-related harms, and this possibility merits systematic research.”
But trends and characteristics of the gambling market, including direct effects from the pandemic, can potentially influence behaviors, too. Most casinos have closed during the pandemic, and most of the sports that people bet on have been canceled or postponed.
“Fewer people are gambling on sports, but they turn then to other areas,” Dr. Potenza said. “If they can’t bet on major league type sports, they might gamble on more local sporting events, or they may bet on other activities going on in society during the pandemic.”
But online gambling poses greater risk.
“Properties of online gambling may constitute a particular health hazard when many people are confined to their homes and have had rapid changes in working conditions, psychosocial stress, anxiety, and depression, as has been described in China,” the paper’s authors wrote. “Online gambling may be particularly concerning due to its availability and velocity” and association with higher debt levels.
In addition to online gaming’s ease and availability, past research has found patients report boredom and escapism as reasons they turned to it.
Again, boredom on its own is not necessarily a problem, but for those who already struggle with addictive behaviors, it can be a trigger, Dr. Kraus said.
“Boredom is very tough for them because it’s often associated with negative emotions,” such as dwelling on things not going well in their lives, he said. “In a pandemic, people are by themselves quite a bit, socially isolated, so for those who are struggling already with some depression or anxiety, it’s only going to be increased.”
Online gaming trends may vary with demographics, however. Dr. Kraus noted that his former clinic at the Veterans Administration has been seeing lower gambling in patients with addictive disorders, but those patients are also older and primarily frequented casinos.
“It’s going to depend on age and familiarity with technology,” he said, but even if older problem gamblers are not going to the Internet now, “let’s wait and see what happens in the next 2 or 3 months.”
The authors noted results from a small survey of patients in treatment for gambling addiction at the Bellvitge University Hospital in Barcelona, Spain, where two of the coauthors work. They conducted telephone surveys with 26 patients about the first 4 weeks of sheltering in place because of the coronavirus. All but four of the patients were male, and their average age was 45 years.
“Most presented worries about increased uncertainties, such as the negative impact on their work, risk of COVID-19 infection of themselves or their loved ones and their treatment,” the authors reported.
Although 19% were completely abstinent, an additional 12% (n = 3) reported worsened gambling. In addition, almost half (46%) reported anxiety symptoms and more than a quarter (27%) had depressive symptoms.
Appropriate care
A particularly complicating factor of the pandemic is how it has disrupted traditional ways of seeking health care, particularly with how much mental health and other medical care has shifted to telehealth and online delivery, Dr. Potenza pointed out.
“This is a change for many people, and it’s important for both caretakers and people in treatment to be mindful of this and to try to ensure that appropriate services are maintained for people during this time,” he said.
For example, 12-step programs traditionally meet in person, which is largely impossible during the pandemic. Some have moved meetings online, and other programs have turned to apps, such as the Addiction Policy Forum’s app Connections, an empirically validated digital therapy platform that lets patients and clinicians remain connected with remote check-ins.
The move to more telehealth may actually increase access, suggested Dr. Hodgins.
“There is no evidence that this is less effective, and in fact, its convenience might be an advantage in reaching more people,” he said. “More challenging is offering group therapies remotely, but this is also feasible.”
The treatment with the strongest evidence remains cognitive-behavioral therapy (CBT), Dr. Hodgins said.
“This therapy, in part, helps people become aware of their erroneous cognitions and to challenge them, but also helps people restructure their activities to change their habits,” he said. He also noted the rise of online therapy, whether supported by a therapist or entirely self-directed, such as Gambling Self-help.
“These programs typically provide cognitive behavior content but also content that comes from studying how people recover from gambling problems,” he said. “The challenge of completely self-directed approaches is follow-through. Like most online content, people tend to flit around more than they might in therapy.” Still, he added, research has shown good outcomes from these programs.
Dr. Potenza also noted that several organizations, including the International Society of Addiction Medicine and Children and Screens, have been hosting webinars related to COVID-19 coping and/or addiction that clinicians and patients might find helpful.
Identification of problematic behaviors
One challenge in watching for problematic gambling behaviors during the pandemic is the set of unusual living circumstances for most people right now. At almost no other time in history have people been primarily confined to their homes, many unable to go to work or working from home, with extra leisure time and nowhere to go.
“With the COVID-19 pandemic, a lot of daily life has changed,” Dr. Potenza said. “It’s unclear whether certain behaviors that have become habitual during the pandemic, such as gaming or online gambling, will then interfere with daily life when the pandemic subsides.”
“The problem is, a small proportion of people who are very vulnerable will develop a disorder and might maintain it,” Dr. Kraus said. Those who already struggle with mental health and may be out of work have greater potential for problematic behaviors.
Dr. Potenza collaborated with other psychiatrists in drafting consensus guidelines on maintaining healthy use of the Internet specifically during the pandemic (Compr Psychiatry. 2020 Jul. doi: 10.10161/comppsych.2020.152180).
“It’s important to think about where one draws the line between normative everyday behaviors – behaviors that are not interfering with life functioning – and those that do interfere with life functioning,” Dr. Potenza said. “If someone is having difficulty making work or family or school obligations, these are important signs that the behavior may be problematic.”
He offered suggestions for things people can do to promote their health during the pandemic, such as having regular routines that include getting physical exercise and social interaction, dining with family if isolating together, and making time for self-care. He also recommended setting limits on the use of digital devices and aiming for a healthy balance in keeping up with the news. The idea is to stay aware of what’s happening without getting burned out or traumatized by news coverage.
Guidance for clinicians
An urgent need for research and guidelines related to gambling and the pandemic exists, the authors argued.
In the meantime, aside from various validated screeners available, Dr. Kraus offered some practical advice for clinicians checking in with their patients: “Ask your patients what they have been doing to cope with this difficult time.”
Some might mention their faith, family, or friends, and others might not have an answer or mention drinking, gaming, or engaging in other activities. “We all do things to cope. Sometimes you use healthy coping and sometimes you use unhealthy coping,” Dr. Kraus said. “I would have a dialogue with my patients around, ‘How are you getting through? What’s helping you? What are some things you’ve tried that are tripping you up?’ ”
If gambling in particular is a possible concern, he encouraged clinicians to ask their patients whether they have tried to quit or what would happen if they stopped gambling.
“What we’d expect is the problem gamblers will have more irritability, crankiness, difficulty with quitting,” he said.
Dr. Hodgins agreed that checking in on how patients’ lives and activities have changed, and their emotion reactions to those changes, is prudent.
“The change in activities might be healthy or might include increased addictive behaviors, including increased use of substances, gaming, pornography, food, and gambling,” he said.
In addition, the paper authors list several examples of guidelines that might be considered in drafting guidance for clinicians, including the following:
- Limiting the extent of gambling
- Not gambling to regulate negative emotions
- Not gambling in order to try to solve financial problems or financial concerns
- Not gambling under the influence of alcohol or drugs
- Carefully monitoring gambling-related time and financial expenditures
- Maintaining and establishing daily routines involving activities other than gambling
- Minding gambling-related attitudes and behaviors in the presence of minors
- Not starting to gamble because of stressors
The research did not receive external funding. Dr. Håkansson has received research funding from the Swedish Sport Foundation, the Swedish alcohol monopoly Systembolaget, and the Swedish state-owned gambling operator AB Svenska Spel. He is working with the company Kontigo Care on devices for gambling addiction follow-up care. Dr. Potenza has received consulting or advisory compensation from several entities, including the Addiction Policy Forum, AXA Gaming, Idorsia, Opiant, and RiverMend Health. Dr. Potenza has received research funding from Mohegan Sun casino and the National Center for Responsible Gaming. No other authors or outside sources had industry-related disclosures.
SOURCE: Håkansson A et al. J Addict Med. 2020 May 18. doi: 10.1097/ADM.0000000000000690.
FROM THE JOURNAL OF ADDICTION MEDICINE
Today’s top news highlights: Addressing racism in maternity care, group forms to protect health professionals from retaliation
Here are the stories our MDedge editors across specialties think you need to know about today:
Addressing racism in the maternal mortality crisis
The emerging racial disparities in COVID-19 incidence and outcomes in the United States are on a collision course with long-standing racial disparities in U.S. maternal care and mortality. “The saying is that ‘the virus doesn’t discriminate,’ but it understands our biases, right? So, the virus takes advantage of the weaknesses in our system,” said Joia A. Crear-Perry, MD, an ob.gyn. and founder and president of the National Birth Equity Collaborative, a New Orleans–based research, training, and advocacy organization working to optimize black maternal and infant health. This article is part of an ongoing feature series on the crisis in maternal mortality in the United States. Here we explore potential solutions for addressing the inequities as proposed by thought leaders and key stakeholders. Read more.
A ‘Beacon’ for physicians, nurses facing retaliation
Sejal Hathi, MD, and two colleagues had long kicked around the idea of starting a nonprofit group that would center on civic and legal advocacy. Once the COVID-19 pandemic hit, the three friends – who have a mix of legal, medical, and advocacy backgrounds – began chatting by email and through Zoom video meetings about how to make the plan a reality. The new organization – named Beacon – quickly mobilized, assembled their team, and launched a website. Beacon’s first project now aims to highlight and protect the legal rights of medical professionals who speak out about personal protection equipment supply and other matters of public concern related to coronavirus. “There are a flurry of reports coming our way about physicians and nurses, as well as other health care workers, who are for whatever reason being disciplined or retaliated against for simply seeking appropriate safety policies at their workplaces,” Dr. Hathi said. “What we’ve found is that many of them don’t even know what their options look like. Doctors, nurses, health care workers are not the typical type to engage politically, to speak out, [or to] advocate for themselves.” Read more.
COVID-19 ravages the Navajo Nation
The Navajo Nation has the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths. These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average rates of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%. “We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language), is a monster confronting the Navajo today. It has had significant impact on our nation and people,” Mary Hasbah Roessel, MD, a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., wrote in a commentary on MDedge. Read more.
Heart pump system authorized for COVID-19 patients
The Food and Drug Administration issued an emergency use authorization (EUA) for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation. The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including pulmonary embolism. Read more.
Deprescribing hypertension meds looks safe for older adults
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure control, researchers concluded based on findings from a randomized multicenter trial. The study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” said James P. Sheppard, PhD, of University of Oxford (England). The report was published in JAMA. Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
Addressing racism in the maternal mortality crisis
The emerging racial disparities in COVID-19 incidence and outcomes in the United States are on a collision course with long-standing racial disparities in U.S. maternal care and mortality. “The saying is that ‘the virus doesn’t discriminate,’ but it understands our biases, right? So, the virus takes advantage of the weaknesses in our system,” said Joia A. Crear-Perry, MD, an ob.gyn. and founder and president of the National Birth Equity Collaborative, a New Orleans–based research, training, and advocacy organization working to optimize black maternal and infant health. This article is part of an ongoing feature series on the crisis in maternal mortality in the United States. Here we explore potential solutions for addressing the inequities as proposed by thought leaders and key stakeholders. Read more.
A ‘Beacon’ for physicians, nurses facing retaliation
Sejal Hathi, MD, and two colleagues had long kicked around the idea of starting a nonprofit group that would center on civic and legal advocacy. Once the COVID-19 pandemic hit, the three friends – who have a mix of legal, medical, and advocacy backgrounds – began chatting by email and through Zoom video meetings about how to make the plan a reality. The new organization – named Beacon – quickly mobilized, assembled their team, and launched a website. Beacon’s first project now aims to highlight and protect the legal rights of medical professionals who speak out about personal protection equipment supply and other matters of public concern related to coronavirus. “There are a flurry of reports coming our way about physicians and nurses, as well as other health care workers, who are for whatever reason being disciplined or retaliated against for simply seeking appropriate safety policies at their workplaces,” Dr. Hathi said. “What we’ve found is that many of them don’t even know what their options look like. Doctors, nurses, health care workers are not the typical type to engage politically, to speak out, [or to] advocate for themselves.” Read more.
COVID-19 ravages the Navajo Nation
The Navajo Nation has the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths. These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average rates of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%. “We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language), is a monster confronting the Navajo today. It has had significant impact on our nation and people,” Mary Hasbah Roessel, MD, a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., wrote in a commentary on MDedge. Read more.
Heart pump system authorized for COVID-19 patients
The Food and Drug Administration issued an emergency use authorization (EUA) for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation. The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including pulmonary embolism. Read more.
Deprescribing hypertension meds looks safe for older adults
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure control, researchers concluded based on findings from a randomized multicenter trial. The study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” said James P. Sheppard, PhD, of University of Oxford (England). The report was published in JAMA. Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
Addressing racism in the maternal mortality crisis
The emerging racial disparities in COVID-19 incidence and outcomes in the United States are on a collision course with long-standing racial disparities in U.S. maternal care and mortality. “The saying is that ‘the virus doesn’t discriminate,’ but it understands our biases, right? So, the virus takes advantage of the weaknesses in our system,” said Joia A. Crear-Perry, MD, an ob.gyn. and founder and president of the National Birth Equity Collaborative, a New Orleans–based research, training, and advocacy organization working to optimize black maternal and infant health. This article is part of an ongoing feature series on the crisis in maternal mortality in the United States. Here we explore potential solutions for addressing the inequities as proposed by thought leaders and key stakeholders. Read more.
A ‘Beacon’ for physicians, nurses facing retaliation
Sejal Hathi, MD, and two colleagues had long kicked around the idea of starting a nonprofit group that would center on civic and legal advocacy. Once the COVID-19 pandemic hit, the three friends – who have a mix of legal, medical, and advocacy backgrounds – began chatting by email and through Zoom video meetings about how to make the plan a reality. The new organization – named Beacon – quickly mobilized, assembled their team, and launched a website. Beacon’s first project now aims to highlight and protect the legal rights of medical professionals who speak out about personal protection equipment supply and other matters of public concern related to coronavirus. “There are a flurry of reports coming our way about physicians and nurses, as well as other health care workers, who are for whatever reason being disciplined or retaliated against for simply seeking appropriate safety policies at their workplaces,” Dr. Hathi said. “What we’ve found is that many of them don’t even know what their options look like. Doctors, nurses, health care workers are not the typical type to engage politically, to speak out, [or to] advocate for themselves.” Read more.
COVID-19 ravages the Navajo Nation
The Navajo Nation has the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths. These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average rates of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%. “We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language), is a monster confronting the Navajo today. It has had significant impact on our nation and people,” Mary Hasbah Roessel, MD, a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., wrote in a commentary on MDedge. Read more.
Heart pump system authorized for COVID-19 patients
The Food and Drug Administration issued an emergency use authorization (EUA) for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation. The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including pulmonary embolism. Read more.
Deprescribing hypertension meds looks safe for older adults
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure control, researchers concluded based on findings from a randomized multicenter trial. The study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” said James P. Sheppard, PhD, of University of Oxford (England). The report was published in JAMA. Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Low IgG levels in COPD patients linked to increased risk of hospitalization
Among patients with COPD, the presence of hypogammaglobulinemia confers a nearly 30% increased risk of hospitalization, results from a pooled analysis of four studies showed.
“Mechanistic studies are still warranted to better elucidate how IgG and other immunoglobulins, in particular IgA, may contribute to the local airway host defense,” researchers led by Fernando Sergio Leitao Filho, MD, PhD, wrote in a study published in Chest (2020 May 18. doi: 10.1016/j.chest.2020.04.058). “Nevertheless, our results raise the possibility that, in select COPD patients, IgG replacement therapy may be effective in reducing the risk of COPD hospitalizations. Given the growing rate of COPD hospitalization in the U.S. and elsewhere, there is a pressing need for a large well-designed trial to test this hypothesis.”
In an effort to evaluate the effect of IgG levels on the cumulative incidence of COPD hospitalizations, Dr. Leitao Filho, of the University of British Columbia, Vancouver, and colleagues drew from 2,259 patients who participated in four different trials: Azithromycin for Prevention of Exacerbations of COPD (MACRO), Simvastatin for the Prevention of Exacerbations in Moderate and Severe COPD (STATCOPE), the Long-Term Oxygen Treatment Trial (LOTT), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE). The mean baseline age of study participants was 66 years, and 641 (28.4%) had hypogammaglobulinemia, which was defined as having a serum IgG levels of less than 7.0 g/L, while the remainder had normal IgG levels.
The pooled meta-analysis, which is believed to be the largest of its kind, revealed that the presence of hypogammaglobulinemia was associated with an incidence of COPD hospitalizations that was 1.29-fold higher than that observed among participants who had normal IgG levels (P = .01). The incidence was even higher among patients with prior COPD admissions (pooled subdistribution hazard ratio, 1.58; P < .01), yet the risk of COPD admissions was similar between IgG groups in patients with no prior hospitalizations (pooled SHR, 1.15; P = .34). Patients with hypogammaglobulinemia also showed significantly higher rates of COPD hospitalizations per person-year, compared with their counterparts who had normal IgG levels (0.48 vs. 0.29, respectively; P < .001.)
The authors acknowledged certain limitations of the study, including the fact that they measured serum IgG levels only at baseline “when participants were clinically stable; thus, the variability of IgG levels in a given individual over time and during the course of an AECOPD [severe acute exacerbation of COPD] is uncertain. Secondly, clinical data on corticosteroid use (formulations, dose, and length of use) were not readily available. However, systemic steroid use (one or more courses due to AECOPD prior to study entry) was accounted for in our analyses.”
The MACRO, STATCOPE, LOTT trials, and the CASCADE cohort were supported by the National Heart, Lung, and Blood Institute; National Institutes of Health; and Department of Health & Human Services. The current study was funded by the Canadian Institutes of Health Research and BC Lung Association. The authors reported having no relevant disclosures.
SOURCE: Leitao Filho SF et al. Chest. 2020 May 18. doi: 10.1016/j.chest.2020.04.058.
Among patients with COPD, the presence of hypogammaglobulinemia confers a nearly 30% increased risk of hospitalization, results from a pooled analysis of four studies showed.
“Mechanistic studies are still warranted to better elucidate how IgG and other immunoglobulins, in particular IgA, may contribute to the local airway host defense,” researchers led by Fernando Sergio Leitao Filho, MD, PhD, wrote in a study published in Chest (2020 May 18. doi: 10.1016/j.chest.2020.04.058). “Nevertheless, our results raise the possibility that, in select COPD patients, IgG replacement therapy may be effective in reducing the risk of COPD hospitalizations. Given the growing rate of COPD hospitalization in the U.S. and elsewhere, there is a pressing need for a large well-designed trial to test this hypothesis.”
In an effort to evaluate the effect of IgG levels on the cumulative incidence of COPD hospitalizations, Dr. Leitao Filho, of the University of British Columbia, Vancouver, and colleagues drew from 2,259 patients who participated in four different trials: Azithromycin for Prevention of Exacerbations of COPD (MACRO), Simvastatin for the Prevention of Exacerbations in Moderate and Severe COPD (STATCOPE), the Long-Term Oxygen Treatment Trial (LOTT), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE). The mean baseline age of study participants was 66 years, and 641 (28.4%) had hypogammaglobulinemia, which was defined as having a serum IgG levels of less than 7.0 g/L, while the remainder had normal IgG levels.
The pooled meta-analysis, which is believed to be the largest of its kind, revealed that the presence of hypogammaglobulinemia was associated with an incidence of COPD hospitalizations that was 1.29-fold higher than that observed among participants who had normal IgG levels (P = .01). The incidence was even higher among patients with prior COPD admissions (pooled subdistribution hazard ratio, 1.58; P < .01), yet the risk of COPD admissions was similar between IgG groups in patients with no prior hospitalizations (pooled SHR, 1.15; P = .34). Patients with hypogammaglobulinemia also showed significantly higher rates of COPD hospitalizations per person-year, compared with their counterparts who had normal IgG levels (0.48 vs. 0.29, respectively; P < .001.)
The authors acknowledged certain limitations of the study, including the fact that they measured serum IgG levels only at baseline “when participants were clinically stable; thus, the variability of IgG levels in a given individual over time and during the course of an AECOPD [severe acute exacerbation of COPD] is uncertain. Secondly, clinical data on corticosteroid use (formulations, dose, and length of use) were not readily available. However, systemic steroid use (one or more courses due to AECOPD prior to study entry) was accounted for in our analyses.”
The MACRO, STATCOPE, LOTT trials, and the CASCADE cohort were supported by the National Heart, Lung, and Blood Institute; National Institutes of Health; and Department of Health & Human Services. The current study was funded by the Canadian Institutes of Health Research and BC Lung Association. The authors reported having no relevant disclosures.
SOURCE: Leitao Filho SF et al. Chest. 2020 May 18. doi: 10.1016/j.chest.2020.04.058.
Among patients with COPD, the presence of hypogammaglobulinemia confers a nearly 30% increased risk of hospitalization, results from a pooled analysis of four studies showed.
“Mechanistic studies are still warranted to better elucidate how IgG and other immunoglobulins, in particular IgA, may contribute to the local airway host defense,” researchers led by Fernando Sergio Leitao Filho, MD, PhD, wrote in a study published in Chest (2020 May 18. doi: 10.1016/j.chest.2020.04.058). “Nevertheless, our results raise the possibility that, in select COPD patients, IgG replacement therapy may be effective in reducing the risk of COPD hospitalizations. Given the growing rate of COPD hospitalization in the U.S. and elsewhere, there is a pressing need for a large well-designed trial to test this hypothesis.”
In an effort to evaluate the effect of IgG levels on the cumulative incidence of COPD hospitalizations, Dr. Leitao Filho, of the University of British Columbia, Vancouver, and colleagues drew from 2,259 patients who participated in four different trials: Azithromycin for Prevention of Exacerbations of COPD (MACRO), Simvastatin for the Prevention of Exacerbations in Moderate and Severe COPD (STATCOPE), the Long-Term Oxygen Treatment Trial (LOTT), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE). The mean baseline age of study participants was 66 years, and 641 (28.4%) had hypogammaglobulinemia, which was defined as having a serum IgG levels of less than 7.0 g/L, while the remainder had normal IgG levels.
The pooled meta-analysis, which is believed to be the largest of its kind, revealed that the presence of hypogammaglobulinemia was associated with an incidence of COPD hospitalizations that was 1.29-fold higher than that observed among participants who had normal IgG levels (P = .01). The incidence was even higher among patients with prior COPD admissions (pooled subdistribution hazard ratio, 1.58; P < .01), yet the risk of COPD admissions was similar between IgG groups in patients with no prior hospitalizations (pooled SHR, 1.15; P = .34). Patients with hypogammaglobulinemia also showed significantly higher rates of COPD hospitalizations per person-year, compared with their counterparts who had normal IgG levels (0.48 vs. 0.29, respectively; P < .001.)
The authors acknowledged certain limitations of the study, including the fact that they measured serum IgG levels only at baseline “when participants were clinically stable; thus, the variability of IgG levels in a given individual over time and during the course of an AECOPD [severe acute exacerbation of COPD] is uncertain. Secondly, clinical data on corticosteroid use (formulations, dose, and length of use) were not readily available. However, systemic steroid use (one or more courses due to AECOPD prior to study entry) was accounted for in our analyses.”
The MACRO, STATCOPE, LOTT trials, and the CASCADE cohort were supported by the National Heart, Lung, and Blood Institute; National Institutes of Health; and Department of Health & Human Services. The current study was funded by the Canadian Institutes of Health Research and BC Lung Association. The authors reported having no relevant disclosures.
SOURCE: Leitao Filho SF et al. Chest. 2020 May 18. doi: 10.1016/j.chest.2020.04.058.
FROM CHEST
Deprescribing hypertension meds can be safe in older patients
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure (BP) control, researchers concluded based on their randomized multicenter trial.
Deprescription of one of at least two antihypertensive meds in such patients was found noninferior to usual care in keeping systolic BP below 150 mm Hg at 12 weeks, in the study that randomly assigned only patients who were considered appropriate for BP-med reduction by their primary care physicians.
Major trials that have shaped some contemporary hypertension guidelines, notably SPRINT, in general have not included such older patients with hypertension along with other chronic conditions, such as diabetes or a history of stroke. So “it’s difficult to know whether their data are relevant for frail, multimorbid patients. In fact, the guidelines say you should use some clinical judgment when applying the results of SPRINT to the kind of patients seen in clinical practice,” James P. Sheppard, PhD, of University of Oxford (England) said in an interview.
The current study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” Dr. Sheppard said.
The trial is meant to provide something of an otherwise-scant evidence base for how to deprescribe antihypertensive medications, said Dr. Sheppard, who is lead author on the report published May 25 in JAMA.
Of the trial’s 282 patients randomly assigned to the drug-reduction group, 86.4% reached the primary endpoint goal of systolic BP less than 150 mm Hg, compared with 87.7% of the 287 patients on usual care, a difference which in adjusted analysis met the predetermined standard for noninferiority.
The intervention group reduced its number of antihypertensive agents by a mean of 0.6 per patient, which the authors described as “a modest reduction.” However, they noted, drugs that were taken away could be reintroduced as judged necessary by the physicians, yet most of the group sustained their reductions until the end of the 12 weeks.
Had the primary endpoint instead specified a threshold of 130 mm Hg for BP control, which is more consistent with SPRINT and some guidelines in the United States, “the deprescribing strategy would have failed to be considered noninferior to usual care” as calculated by the OPTIMISE authors themselves, observed an accompanying editorial.
The 150 mm Hg threshold chosen by the trialists for the primary endpoint, therefore, “was somewhat of a low bar,” wrote Eric D. Peterson, MD, MPH, of Duke University, Durham, N.C., and Michael W. Rich, MD, of Washington University School of Medicine, St. Louis, Mo.
“Here in the UK it wouldn’t be considered a low bar,” Dr. Sheppard said in an interview. The National Institute for Health and Care Excellence guidelines in Britain “recommends that you treat people over the age of 18 regardless of whether they have any other conditions and to 150 mm Hg systolic.”
The study’s general practitioners, he said, “did what we told them to do, and as a result, two-thirds of the patients were able to reduce their medications. If we had a lower threshold for treatment, it’s possible that more patients might have had medications reintroduced. I think you still could have potentially ended up with a noninferior result.”
Participating physicians were instructed to enroll only “patients who, in their opinion, might potentially benefit from medication reduction due to one or more of the following existing characteristics: polypharmacy, comorbidity, nonadherence or dislike of medicines, or frailty,” the report notes.
They chose which antihypertensives would be dropped for each patient and “were given a medication reduction algorithm to assist with this decision.” Physicians also followed a guide for monitoring for safety issues and were told to reintroduce medications if systolic BP exceeded 150 mm Hg or diastolic BP rose above 90 mm Hg for more than 1 week or in the event of adverse events or signs of accelerated hypertension, the group wrote.
In the deprescription group, the mean systolic BP rose 4.3 points from baseline to 12 weeks, from 129.4 to 133.7 mm Hg. For those given usual care, mean systolic BP went from 130.5 to 130.8 mm Hg. Adjusted, the mean change in systolic BP was 3.4 mm Hg greater (P = .005) in the intervention group. The corresponding adjusted mean change in diastolic BP was a 2.2 mm Hg increase in the intervention group (P = .001).
Although the difference seems minimal, wrote Dr. Peterson and Dr. Rich, “such differences in BP can potentially lead to long-term differences in outcomes at the population level.”
Also, they pointed out, only about 10% of patients screened for enrollment actually entered the study, which brings into question the study’s generalizability, and “patients in the trial had relatively well-controlled BP at baseline.”
Dr. Sheppard said patients in the original screened population, taken from a national database, were directly invited to participate en masse by conventional mail, based on broad inclusion criteria. Far more than the number needed were invited, and nearly all of those excluded from the study had simply not responded to the invitation.
As for greater increases in systolic and diastolic pressures in the deprescribing group, the OPTIMISE authors acknowledged that “caution should be exercised when adopting this approach in routine clinical practice.”
His own view, Dr. Sheppard said, “is that there are some patients who will definitely benefit from intensive blood pressure lowering like you saw in the SPRINT trial. And there’s other patients who will benefit from deprescribing and having a slightly higher target. Those sorts of things very much need to be individualized at the patient level.”
And ideally, he added, clinicians in practice should probably be even more selective in choosing patients for a deprescribing strategy, “and focus on people who are at the highest risk of adverse events.”
Dr. Sheppard has disclosed no relevant financial relationships; disclosures for the other authors are in the report. Dr. Peterson disclosed receiving personal fees from Cerner and Livongo and grants and personal fees from AstraZeneca, Janssen, and Amgen; Dr. Rick has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure (BP) control, researchers concluded based on their randomized multicenter trial.
Deprescription of one of at least two antihypertensive meds in such patients was found noninferior to usual care in keeping systolic BP below 150 mm Hg at 12 weeks, in the study that randomly assigned only patients who were considered appropriate for BP-med reduction by their primary care physicians.
Major trials that have shaped some contemporary hypertension guidelines, notably SPRINT, in general have not included such older patients with hypertension along with other chronic conditions, such as diabetes or a history of stroke. So “it’s difficult to know whether their data are relevant for frail, multimorbid patients. In fact, the guidelines say you should use some clinical judgment when applying the results of SPRINT to the kind of patients seen in clinical practice,” James P. Sheppard, PhD, of University of Oxford (England) said in an interview.
The current study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” Dr. Sheppard said.
The trial is meant to provide something of an otherwise-scant evidence base for how to deprescribe antihypertensive medications, said Dr. Sheppard, who is lead author on the report published May 25 in JAMA.
Of the trial’s 282 patients randomly assigned to the drug-reduction group, 86.4% reached the primary endpoint goal of systolic BP less than 150 mm Hg, compared with 87.7% of the 287 patients on usual care, a difference which in adjusted analysis met the predetermined standard for noninferiority.
The intervention group reduced its number of antihypertensive agents by a mean of 0.6 per patient, which the authors described as “a modest reduction.” However, they noted, drugs that were taken away could be reintroduced as judged necessary by the physicians, yet most of the group sustained their reductions until the end of the 12 weeks.
Had the primary endpoint instead specified a threshold of 130 mm Hg for BP control, which is more consistent with SPRINT and some guidelines in the United States, “the deprescribing strategy would have failed to be considered noninferior to usual care” as calculated by the OPTIMISE authors themselves, observed an accompanying editorial.
The 150 mm Hg threshold chosen by the trialists for the primary endpoint, therefore, “was somewhat of a low bar,” wrote Eric D. Peterson, MD, MPH, of Duke University, Durham, N.C., and Michael W. Rich, MD, of Washington University School of Medicine, St. Louis, Mo.
“Here in the UK it wouldn’t be considered a low bar,” Dr. Sheppard said in an interview. The National Institute for Health and Care Excellence guidelines in Britain “recommends that you treat people over the age of 18 regardless of whether they have any other conditions and to 150 mm Hg systolic.”
The study’s general practitioners, he said, “did what we told them to do, and as a result, two-thirds of the patients were able to reduce their medications. If we had a lower threshold for treatment, it’s possible that more patients might have had medications reintroduced. I think you still could have potentially ended up with a noninferior result.”
Participating physicians were instructed to enroll only “patients who, in their opinion, might potentially benefit from medication reduction due to one or more of the following existing characteristics: polypharmacy, comorbidity, nonadherence or dislike of medicines, or frailty,” the report notes.
They chose which antihypertensives would be dropped for each patient and “were given a medication reduction algorithm to assist with this decision.” Physicians also followed a guide for monitoring for safety issues and were told to reintroduce medications if systolic BP exceeded 150 mm Hg or diastolic BP rose above 90 mm Hg for more than 1 week or in the event of adverse events or signs of accelerated hypertension, the group wrote.
In the deprescription group, the mean systolic BP rose 4.3 points from baseline to 12 weeks, from 129.4 to 133.7 mm Hg. For those given usual care, mean systolic BP went from 130.5 to 130.8 mm Hg. Adjusted, the mean change in systolic BP was 3.4 mm Hg greater (P = .005) in the intervention group. The corresponding adjusted mean change in diastolic BP was a 2.2 mm Hg increase in the intervention group (P = .001).
Although the difference seems minimal, wrote Dr. Peterson and Dr. Rich, “such differences in BP can potentially lead to long-term differences in outcomes at the population level.”
Also, they pointed out, only about 10% of patients screened for enrollment actually entered the study, which brings into question the study’s generalizability, and “patients in the trial had relatively well-controlled BP at baseline.”
Dr. Sheppard said patients in the original screened population, taken from a national database, were directly invited to participate en masse by conventional mail, based on broad inclusion criteria. Far more than the number needed were invited, and nearly all of those excluded from the study had simply not responded to the invitation.
As for greater increases in systolic and diastolic pressures in the deprescribing group, the OPTIMISE authors acknowledged that “caution should be exercised when adopting this approach in routine clinical practice.”
His own view, Dr. Sheppard said, “is that there are some patients who will definitely benefit from intensive blood pressure lowering like you saw in the SPRINT trial. And there’s other patients who will benefit from deprescribing and having a slightly higher target. Those sorts of things very much need to be individualized at the patient level.”
And ideally, he added, clinicians in practice should probably be even more selective in choosing patients for a deprescribing strategy, “and focus on people who are at the highest risk of adverse events.”
Dr. Sheppard has disclosed no relevant financial relationships; disclosures for the other authors are in the report. Dr. Peterson disclosed receiving personal fees from Cerner and Livongo and grants and personal fees from AstraZeneca, Janssen, and Amgen; Dr. Rick has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure (BP) control, researchers concluded based on their randomized multicenter trial.
Deprescription of one of at least two antihypertensive meds in such patients was found noninferior to usual care in keeping systolic BP below 150 mm Hg at 12 weeks, in the study that randomly assigned only patients who were considered appropriate for BP-med reduction by their primary care physicians.
Major trials that have shaped some contemporary hypertension guidelines, notably SPRINT, in general have not included such older patients with hypertension along with other chronic conditions, such as diabetes or a history of stroke. So “it’s difficult to know whether their data are relevant for frail, multimorbid patients. In fact, the guidelines say you should use some clinical judgment when applying the results of SPRINT to the kind of patients seen in clinical practice,” James P. Sheppard, PhD, of University of Oxford (England) said in an interview.
The current study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” Dr. Sheppard said.
The trial is meant to provide something of an otherwise-scant evidence base for how to deprescribe antihypertensive medications, said Dr. Sheppard, who is lead author on the report published May 25 in JAMA.
Of the trial’s 282 patients randomly assigned to the drug-reduction group, 86.4% reached the primary endpoint goal of systolic BP less than 150 mm Hg, compared with 87.7% of the 287 patients on usual care, a difference which in adjusted analysis met the predetermined standard for noninferiority.
The intervention group reduced its number of antihypertensive agents by a mean of 0.6 per patient, which the authors described as “a modest reduction.” However, they noted, drugs that were taken away could be reintroduced as judged necessary by the physicians, yet most of the group sustained their reductions until the end of the 12 weeks.
Had the primary endpoint instead specified a threshold of 130 mm Hg for BP control, which is more consistent with SPRINT and some guidelines in the United States, “the deprescribing strategy would have failed to be considered noninferior to usual care” as calculated by the OPTIMISE authors themselves, observed an accompanying editorial.
The 150 mm Hg threshold chosen by the trialists for the primary endpoint, therefore, “was somewhat of a low bar,” wrote Eric D. Peterson, MD, MPH, of Duke University, Durham, N.C., and Michael W. Rich, MD, of Washington University School of Medicine, St. Louis, Mo.
“Here in the UK it wouldn’t be considered a low bar,” Dr. Sheppard said in an interview. The National Institute for Health and Care Excellence guidelines in Britain “recommends that you treat people over the age of 18 regardless of whether they have any other conditions and to 150 mm Hg systolic.”
The study’s general practitioners, he said, “did what we told them to do, and as a result, two-thirds of the patients were able to reduce their medications. If we had a lower threshold for treatment, it’s possible that more patients might have had medications reintroduced. I think you still could have potentially ended up with a noninferior result.”
Participating physicians were instructed to enroll only “patients who, in their opinion, might potentially benefit from medication reduction due to one or more of the following existing characteristics: polypharmacy, comorbidity, nonadherence or dislike of medicines, or frailty,” the report notes.
They chose which antihypertensives would be dropped for each patient and “were given a medication reduction algorithm to assist with this decision.” Physicians also followed a guide for monitoring for safety issues and were told to reintroduce medications if systolic BP exceeded 150 mm Hg or diastolic BP rose above 90 mm Hg for more than 1 week or in the event of adverse events or signs of accelerated hypertension, the group wrote.
In the deprescription group, the mean systolic BP rose 4.3 points from baseline to 12 weeks, from 129.4 to 133.7 mm Hg. For those given usual care, mean systolic BP went from 130.5 to 130.8 mm Hg. Adjusted, the mean change in systolic BP was 3.4 mm Hg greater (P = .005) in the intervention group. The corresponding adjusted mean change in diastolic BP was a 2.2 mm Hg increase in the intervention group (P = .001).
Although the difference seems minimal, wrote Dr. Peterson and Dr. Rich, “such differences in BP can potentially lead to long-term differences in outcomes at the population level.”
Also, they pointed out, only about 10% of patients screened for enrollment actually entered the study, which brings into question the study’s generalizability, and “patients in the trial had relatively well-controlled BP at baseline.”
Dr. Sheppard said patients in the original screened population, taken from a national database, were directly invited to participate en masse by conventional mail, based on broad inclusion criteria. Far more than the number needed were invited, and nearly all of those excluded from the study had simply not responded to the invitation.
As for greater increases in systolic and diastolic pressures in the deprescribing group, the OPTIMISE authors acknowledged that “caution should be exercised when adopting this approach in routine clinical practice.”
His own view, Dr. Sheppard said, “is that there are some patients who will definitely benefit from intensive blood pressure lowering like you saw in the SPRINT trial. And there’s other patients who will benefit from deprescribing and having a slightly higher target. Those sorts of things very much need to be individualized at the patient level.”
And ideally, he added, clinicians in practice should probably be even more selective in choosing patients for a deprescribing strategy, “and focus on people who are at the highest risk of adverse events.”
Dr. Sheppard has disclosed no relevant financial relationships; disclosures for the other authors are in the report. Dr. Peterson disclosed receiving personal fees from Cerner and Livongo and grants and personal fees from AstraZeneca, Janssen, and Amgen; Dr. Rick has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
COVID-19: New group stands up for health professionals facing retaliation
Sejal Hathi, MD, and two colleagues had long kicked around the idea of starting a nonprofit group that would center on civic and legal advocacy.
Once the COVID-19 pandemic hit, the three friends – who have a mix of legal, medical, and advocacy backgrounds – began chatting by email and through Zoom video meetings about how to make the plan a reality.
“When COVID came around, we began talking about where we could make a difference and help people where help was needed most,” said Dr. Hathi, an internal medicine resident at Massachusetts General Hospital in Boston. “We decided the PPE issue makes a good first focus.”
The new organization – named Beacon – quickly mobilized, assembled their team, and launched a website. Beacon’s first project now aims to highlight and protect the legal rights of medical professionals who speak out about personal protection equipment (PPE) supply and other matters of public concern related to coronavirus.
In recent months, health care professionals have reported being reprimanded or even terminated for publicly discussing PPE shortages or sharing safety concerns. Other clinicians say they can’t share their experiences for fear of reprisal by their hospitals.
“The centrality of adequate PPE is pretty undeniable at this point,” said John Paul Schnapper-Casteras, JD, an attorney and cofounder of the organization. “In terms of speaking up about matters of workplace safety and public concern, when health care workers share knowledge, correct problems – and in some cases, blow the whistle – it affirmatively benefits medical science, disease control, and the public interest,” he said in an interview. “We have seen in other countries, the disastrous consequences that can stem from silencing medical professionals who try to speak out.”
Letter highlights hospitals’ obligations
As part of their efforts, Beacon leaders drafted a strongly worded letter on behalf of health care workers outlining the legal obligations of hospitals to ensure workplace safety, underscoring the federal protections that bar retaliation against employees who exercise their workplace rights. Whistleblower protections under the Occupational Safety and Health Act, the False Claims Act, and the National Labor Relations Act, for instance, prohibit retaliation against employees for blowing the whistle on unsafe or unlawful conditions.
Beacon’s letter urges hospitals to adopt a uniform policy that recognizes “the importance and legitimacy of doctors, nurses, and medical professionals who research, write, and speak about the use and supply of PPE in addressing coronavirus.”
“We are deeply troubled by reports that medical professionals are being fired, retaliated against, disciplined, or threatened for speaking (or potentially speaking) about PPE shortages and related safety conditions that directly place their and their patients’ lives in danger,” the letter states. “As a matter of law, medical personnel have a wide range of rights that protect their employment status and ability to comment on matters of public concern (and provide a cause of action in court if these rights are violated).”
Dr. Hathi, who over the last decade has founded two social enterprises advancing women’s rights, said organizers have sent the letter to hospitals and health systems that were publicly reported or otherwise known to have threatened, terminated, or retaliated against employees for protesting PPE shortages or speaking up about unsafe working conditions during this crisis. The letter is available on the Beacon website.
“Many letters have been written [recently] criticizing hospitals for retaliating against their workers,” Dr. Hathi said. “Ours amplifies this voice. But it also serves as a tool for self-empowerment, a stark warning to health systems that their actions bear consequences, and an assurance to health workers across the country that we’re listening and we’re here to help them safeguard their rights and their dignity at work.”
Dr. Hathi and her colleagues have also circulated the letter on social media and other platforms as a petition that health care professionals and others can sign in support of fair and safe treatment of employees with respect to PPE. So far, the group has collected signatures from individuals, communities, and organizations representing about 35,000 people, Dr. Hathi said.
Workplace rights, legal options
Beacon leaders have also begun counseling and advising health care workers who have experienced retaliation or discipline associated with PPE issues. Educating medical professionals about their workplace rights and legal options is another key focus of the group, according to its founders.
“There are a flurry of reports coming our way about physicians and nurses, as well as other health care workers, who are for whatever reason being disciplined or retaliated against for simply seeking appropriate safety policies at their workplaces,” Dr. Hathi said. “What we’ve found is that many of them don’t even know what their options look like. Doctors, nurses, health care workers are not the typical type to engage politically, to speak out, [or to] advocate for themselves.”
In one instance, they heard from a physician who wanted to protect nurses at his hospital because they did not have masks and were being coughed on by COVID-19 patients. The doctor requested that his hospital supply masks to the nurses. After making the request, the physician was disciplined by hospital leadership, Dr. Hathi said. In another case, a physician assistant told the group she was terminated because she wanted to wear her own mask in a hospital that was treating COVID patients.
“She was not allowed to, and she was fired for even bringing it up,” said Sheel Tyle, JD, an attorney and Beacon cofounder.
Beacon intends to assist health care workers who face such retaliation and discipline in a number of ways, Mr. Tyle said. For instance, by helping an individual get compensation for what happened, aiding the professional in getting their job back, or helping the worker retain a severance package of some kind, he said.
“And then there is the larger public policy issue of preventing the hospital from being a bad actor,” Mr. Tyle said. “That can be done through state or federal complaints, largely under different statutes related to workplace protection or OSHA. Our group [has] lawyers that could represent clients individually as well as a number of friends who are attorneys in various states who we could partner with, depending on the situation.”
While the organization is positioned to represent health professionals in lawsuits if necessary, Mr. Tyle emphasized that litigation is not the intended goal of the group. Rather, they are seeking to deter hospitals and others from being “bad actors,” through any number of methods, including communication, advocacy, or complaints.
Ultimately, Dr. Hathi said she hopes the organization’s efforts activate health care workers as an organizing body and in the process, spark policy change at the federal level to better protect health care workers.
“The challenges we’re facing now – protecting workplace safety, employee voice, a living wage, adequate sick and family leave – long predate this pandemic,” Dr. Hathi said. “But they’ve deepened and acquired existential significance as, battered by policy failures and the unsparing virus itself, physicians shed their political indifference and join a growing nationwide chorus to restore workers’ rights and to fundamentally reimagine our broken healthcare system. Now, more than ever before, organizations like Beacon are vital for arming health workers in this fight.”
Sejal Hathi, MD, and two colleagues had long kicked around the idea of starting a nonprofit group that would center on civic and legal advocacy.
Once the COVID-19 pandemic hit, the three friends – who have a mix of legal, medical, and advocacy backgrounds – began chatting by email and through Zoom video meetings about how to make the plan a reality.
“When COVID came around, we began talking about where we could make a difference and help people where help was needed most,” said Dr. Hathi, an internal medicine resident at Massachusetts General Hospital in Boston. “We decided the PPE issue makes a good first focus.”
The new organization – named Beacon – quickly mobilized, assembled their team, and launched a website. Beacon’s first project now aims to highlight and protect the legal rights of medical professionals who speak out about personal protection equipment (PPE) supply and other matters of public concern related to coronavirus.
In recent months, health care professionals have reported being reprimanded or even terminated for publicly discussing PPE shortages or sharing safety concerns. Other clinicians say they can’t share their experiences for fear of reprisal by their hospitals.
“The centrality of adequate PPE is pretty undeniable at this point,” said John Paul Schnapper-Casteras, JD, an attorney and cofounder of the organization. “In terms of speaking up about matters of workplace safety and public concern, when health care workers share knowledge, correct problems – and in some cases, blow the whistle – it affirmatively benefits medical science, disease control, and the public interest,” he said in an interview. “We have seen in other countries, the disastrous consequences that can stem from silencing medical professionals who try to speak out.”
Letter highlights hospitals’ obligations
As part of their efforts, Beacon leaders drafted a strongly worded letter on behalf of health care workers outlining the legal obligations of hospitals to ensure workplace safety, underscoring the federal protections that bar retaliation against employees who exercise their workplace rights. Whistleblower protections under the Occupational Safety and Health Act, the False Claims Act, and the National Labor Relations Act, for instance, prohibit retaliation against employees for blowing the whistle on unsafe or unlawful conditions.
Beacon’s letter urges hospitals to adopt a uniform policy that recognizes “the importance and legitimacy of doctors, nurses, and medical professionals who research, write, and speak about the use and supply of PPE in addressing coronavirus.”
“We are deeply troubled by reports that medical professionals are being fired, retaliated against, disciplined, or threatened for speaking (or potentially speaking) about PPE shortages and related safety conditions that directly place their and their patients’ lives in danger,” the letter states. “As a matter of law, medical personnel have a wide range of rights that protect their employment status and ability to comment on matters of public concern (and provide a cause of action in court if these rights are violated).”
Dr. Hathi, who over the last decade has founded two social enterprises advancing women’s rights, said organizers have sent the letter to hospitals and health systems that were publicly reported or otherwise known to have threatened, terminated, or retaliated against employees for protesting PPE shortages or speaking up about unsafe working conditions during this crisis. The letter is available on the Beacon website.
“Many letters have been written [recently] criticizing hospitals for retaliating against their workers,” Dr. Hathi said. “Ours amplifies this voice. But it also serves as a tool for self-empowerment, a stark warning to health systems that their actions bear consequences, and an assurance to health workers across the country that we’re listening and we’re here to help them safeguard their rights and their dignity at work.”
Dr. Hathi and her colleagues have also circulated the letter on social media and other platforms as a petition that health care professionals and others can sign in support of fair and safe treatment of employees with respect to PPE. So far, the group has collected signatures from individuals, communities, and organizations representing about 35,000 people, Dr. Hathi said.
Workplace rights, legal options
Beacon leaders have also begun counseling and advising health care workers who have experienced retaliation or discipline associated with PPE issues. Educating medical professionals about their workplace rights and legal options is another key focus of the group, according to its founders.
“There are a flurry of reports coming our way about physicians and nurses, as well as other health care workers, who are for whatever reason being disciplined or retaliated against for simply seeking appropriate safety policies at their workplaces,” Dr. Hathi said. “What we’ve found is that many of them don’t even know what their options look like. Doctors, nurses, health care workers are not the typical type to engage politically, to speak out, [or to] advocate for themselves.”
In one instance, they heard from a physician who wanted to protect nurses at his hospital because they did not have masks and were being coughed on by COVID-19 patients. The doctor requested that his hospital supply masks to the nurses. After making the request, the physician was disciplined by hospital leadership, Dr. Hathi said. In another case, a physician assistant told the group she was terminated because she wanted to wear her own mask in a hospital that was treating COVID patients.
“She was not allowed to, and she was fired for even bringing it up,” said Sheel Tyle, JD, an attorney and Beacon cofounder.
Beacon intends to assist health care workers who face such retaliation and discipline in a number of ways, Mr. Tyle said. For instance, by helping an individual get compensation for what happened, aiding the professional in getting their job back, or helping the worker retain a severance package of some kind, he said.
“And then there is the larger public policy issue of preventing the hospital from being a bad actor,” Mr. Tyle said. “That can be done through state or federal complaints, largely under different statutes related to workplace protection or OSHA. Our group [has] lawyers that could represent clients individually as well as a number of friends who are attorneys in various states who we could partner with, depending on the situation.”
While the organization is positioned to represent health professionals in lawsuits if necessary, Mr. Tyle emphasized that litigation is not the intended goal of the group. Rather, they are seeking to deter hospitals and others from being “bad actors,” through any number of methods, including communication, advocacy, or complaints.
Ultimately, Dr. Hathi said she hopes the organization’s efforts activate health care workers as an organizing body and in the process, spark policy change at the federal level to better protect health care workers.
“The challenges we’re facing now – protecting workplace safety, employee voice, a living wage, adequate sick and family leave – long predate this pandemic,” Dr. Hathi said. “But they’ve deepened and acquired existential significance as, battered by policy failures and the unsparing virus itself, physicians shed their political indifference and join a growing nationwide chorus to restore workers’ rights and to fundamentally reimagine our broken healthcare system. Now, more than ever before, organizations like Beacon are vital for arming health workers in this fight.”
Sejal Hathi, MD, and two colleagues had long kicked around the idea of starting a nonprofit group that would center on civic and legal advocacy.
Once the COVID-19 pandemic hit, the three friends – who have a mix of legal, medical, and advocacy backgrounds – began chatting by email and through Zoom video meetings about how to make the plan a reality.
“When COVID came around, we began talking about where we could make a difference and help people where help was needed most,” said Dr. Hathi, an internal medicine resident at Massachusetts General Hospital in Boston. “We decided the PPE issue makes a good first focus.”
The new organization – named Beacon – quickly mobilized, assembled their team, and launched a website. Beacon’s first project now aims to highlight and protect the legal rights of medical professionals who speak out about personal protection equipment (PPE) supply and other matters of public concern related to coronavirus.
In recent months, health care professionals have reported being reprimanded or even terminated for publicly discussing PPE shortages or sharing safety concerns. Other clinicians say they can’t share their experiences for fear of reprisal by their hospitals.
“The centrality of adequate PPE is pretty undeniable at this point,” said John Paul Schnapper-Casteras, JD, an attorney and cofounder of the organization. “In terms of speaking up about matters of workplace safety and public concern, when health care workers share knowledge, correct problems – and in some cases, blow the whistle – it affirmatively benefits medical science, disease control, and the public interest,” he said in an interview. “We have seen in other countries, the disastrous consequences that can stem from silencing medical professionals who try to speak out.”
Letter highlights hospitals’ obligations
As part of their efforts, Beacon leaders drafted a strongly worded letter on behalf of health care workers outlining the legal obligations of hospitals to ensure workplace safety, underscoring the federal protections that bar retaliation against employees who exercise their workplace rights. Whistleblower protections under the Occupational Safety and Health Act, the False Claims Act, and the National Labor Relations Act, for instance, prohibit retaliation against employees for blowing the whistle on unsafe or unlawful conditions.
Beacon’s letter urges hospitals to adopt a uniform policy that recognizes “the importance and legitimacy of doctors, nurses, and medical professionals who research, write, and speak about the use and supply of PPE in addressing coronavirus.”
“We are deeply troubled by reports that medical professionals are being fired, retaliated against, disciplined, or threatened for speaking (or potentially speaking) about PPE shortages and related safety conditions that directly place their and their patients’ lives in danger,” the letter states. “As a matter of law, medical personnel have a wide range of rights that protect their employment status and ability to comment on matters of public concern (and provide a cause of action in court if these rights are violated).”
Dr. Hathi, who over the last decade has founded two social enterprises advancing women’s rights, said organizers have sent the letter to hospitals and health systems that were publicly reported or otherwise known to have threatened, terminated, or retaliated against employees for protesting PPE shortages or speaking up about unsafe working conditions during this crisis. The letter is available on the Beacon website.
“Many letters have been written [recently] criticizing hospitals for retaliating against their workers,” Dr. Hathi said. “Ours amplifies this voice. But it also serves as a tool for self-empowerment, a stark warning to health systems that their actions bear consequences, and an assurance to health workers across the country that we’re listening and we’re here to help them safeguard their rights and their dignity at work.”
Dr. Hathi and her colleagues have also circulated the letter on social media and other platforms as a petition that health care professionals and others can sign in support of fair and safe treatment of employees with respect to PPE. So far, the group has collected signatures from individuals, communities, and organizations representing about 35,000 people, Dr. Hathi said.
Workplace rights, legal options
Beacon leaders have also begun counseling and advising health care workers who have experienced retaliation or discipline associated with PPE issues. Educating medical professionals about their workplace rights and legal options is another key focus of the group, according to its founders.
“There are a flurry of reports coming our way about physicians and nurses, as well as other health care workers, who are for whatever reason being disciplined or retaliated against for simply seeking appropriate safety policies at their workplaces,” Dr. Hathi said. “What we’ve found is that many of them don’t even know what their options look like. Doctors, nurses, health care workers are not the typical type to engage politically, to speak out, [or to] advocate for themselves.”
In one instance, they heard from a physician who wanted to protect nurses at his hospital because they did not have masks and were being coughed on by COVID-19 patients. The doctor requested that his hospital supply masks to the nurses. After making the request, the physician was disciplined by hospital leadership, Dr. Hathi said. In another case, a physician assistant told the group she was terminated because she wanted to wear her own mask in a hospital that was treating COVID patients.
“She was not allowed to, and she was fired for even bringing it up,” said Sheel Tyle, JD, an attorney and Beacon cofounder.
Beacon intends to assist health care workers who face such retaliation and discipline in a number of ways, Mr. Tyle said. For instance, by helping an individual get compensation for what happened, aiding the professional in getting their job back, or helping the worker retain a severance package of some kind, he said.
“And then there is the larger public policy issue of preventing the hospital from being a bad actor,” Mr. Tyle said. “That can be done through state or federal complaints, largely under different statutes related to workplace protection or OSHA. Our group [has] lawyers that could represent clients individually as well as a number of friends who are attorneys in various states who we could partner with, depending on the situation.”
While the organization is positioned to represent health professionals in lawsuits if necessary, Mr. Tyle emphasized that litigation is not the intended goal of the group. Rather, they are seeking to deter hospitals and others from being “bad actors,” through any number of methods, including communication, advocacy, or complaints.
Ultimately, Dr. Hathi said she hopes the organization’s efforts activate health care workers as an organizing body and in the process, spark policy change at the federal level to better protect health care workers.
“The challenges we’re facing now – protecting workplace safety, employee voice, a living wage, adequate sick and family leave – long predate this pandemic,” Dr. Hathi said. “But they’ve deepened and acquired existential significance as, battered by policy failures and the unsparing virus itself, physicians shed their political indifference and join a growing nationwide chorus to restore workers’ rights and to fundamentally reimagine our broken healthcare system. Now, more than ever before, organizations like Beacon are vital for arming health workers in this fight.”
FDA okays emergency use for Impella RP in COVID-19 right heart failure
The Food and Drug Administration issued an emergency use authorization for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation, Abiomed announced June 1.
“Based on extrapolation of data from the approved indication and reported clinical experience, FDA has concluded that the Impella RP may be effective at providing temporary right ventricular support for the treatment of acute right heart failure or decompensation caused by COVID-19 complications, including PE [pulmonary embolism],” the letter noted.
It cited, for example, use of the temporary heart pump in a 59-year-old woman suffering from COVID-19 who went into right ventricular failure and became hypotensive after an acute PE was removed. After placement of the device, the patient experienced a “dramatic and immediate” improvement in arterial pressure and the device was removed on the fifth day, according to Amir Kaki, MD, and Ted Schreiber, MD, of Ascension St. John Hospital, Detroit, whose review of the case has been posted online.
“Acute pulmonary embolism is clearly being recognized as a life-threatening manifestation of COVID-19. Impella RP is an important tool to help cardiologists save lives during this pandemic,” Dr. Kaki said in the letter. “As we have demonstrated in our series of patients, early recognition of right ventricular dysfunction and early placement of the Impella RP for patients who are hypotensive can be lifesaving.”
Other data cited in support of the Impella RP emergency use authorization (EUA) include a 2019 series of hemodynamically unstable patients with PE in Japan and a 2017 case report of a 47-year-old man with right ventricular failure, profound shock, and a massive PE.
The FDA granted premarket approval of the Impella RP system in 2017 to provide temporary right ventricular support for up to 14 days in patients with a body surface area of at least 1.5 m2 who develop acute right heart failure or decompensation following left ventricular assist device implantation, MI, heart transplant, or open-heart surgery.
The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including PE.
The Impella RP is authorized only for emergency use under the EUA and only for the duration of the circumstances justifying use of EUAs, the letter noted.
Last year, concerns were raised about off-indication use after interim results from a postapproval study suggested a higher risk for death than seen in premarket studies treated with the temporary heart pump.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration issued an emergency use authorization for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation, Abiomed announced June 1.
“Based on extrapolation of data from the approved indication and reported clinical experience, FDA has concluded that the Impella RP may be effective at providing temporary right ventricular support for the treatment of acute right heart failure or decompensation caused by COVID-19 complications, including PE [pulmonary embolism],” the letter noted.
It cited, for example, use of the temporary heart pump in a 59-year-old woman suffering from COVID-19 who went into right ventricular failure and became hypotensive after an acute PE was removed. After placement of the device, the patient experienced a “dramatic and immediate” improvement in arterial pressure and the device was removed on the fifth day, according to Amir Kaki, MD, and Ted Schreiber, MD, of Ascension St. John Hospital, Detroit, whose review of the case has been posted online.
“Acute pulmonary embolism is clearly being recognized as a life-threatening manifestation of COVID-19. Impella RP is an important tool to help cardiologists save lives during this pandemic,” Dr. Kaki said in the letter. “As we have demonstrated in our series of patients, early recognition of right ventricular dysfunction and early placement of the Impella RP for patients who are hypotensive can be lifesaving.”
Other data cited in support of the Impella RP emergency use authorization (EUA) include a 2019 series of hemodynamically unstable patients with PE in Japan and a 2017 case report of a 47-year-old man with right ventricular failure, profound shock, and a massive PE.
The FDA granted premarket approval of the Impella RP system in 2017 to provide temporary right ventricular support for up to 14 days in patients with a body surface area of at least 1.5 m2 who develop acute right heart failure or decompensation following left ventricular assist device implantation, MI, heart transplant, or open-heart surgery.
The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including PE.
The Impella RP is authorized only for emergency use under the EUA and only for the duration of the circumstances justifying use of EUAs, the letter noted.
Last year, concerns were raised about off-indication use after interim results from a postapproval study suggested a higher risk for death than seen in premarket studies treated with the temporary heart pump.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration issued an emergency use authorization for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation, Abiomed announced June 1.
“Based on extrapolation of data from the approved indication and reported clinical experience, FDA has concluded that the Impella RP may be effective at providing temporary right ventricular support for the treatment of acute right heart failure or decompensation caused by COVID-19 complications, including PE [pulmonary embolism],” the letter noted.
It cited, for example, use of the temporary heart pump in a 59-year-old woman suffering from COVID-19 who went into right ventricular failure and became hypotensive after an acute PE was removed. After placement of the device, the patient experienced a “dramatic and immediate” improvement in arterial pressure and the device was removed on the fifth day, according to Amir Kaki, MD, and Ted Schreiber, MD, of Ascension St. John Hospital, Detroit, whose review of the case has been posted online.
“Acute pulmonary embolism is clearly being recognized as a life-threatening manifestation of COVID-19. Impella RP is an important tool to help cardiologists save lives during this pandemic,” Dr. Kaki said in the letter. “As we have demonstrated in our series of patients, early recognition of right ventricular dysfunction and early placement of the Impella RP for patients who are hypotensive can be lifesaving.”
Other data cited in support of the Impella RP emergency use authorization (EUA) include a 2019 series of hemodynamically unstable patients with PE in Japan and a 2017 case report of a 47-year-old man with right ventricular failure, profound shock, and a massive PE.
The FDA granted premarket approval of the Impella RP system in 2017 to provide temporary right ventricular support for up to 14 days in patients with a body surface area of at least 1.5 m2 who develop acute right heart failure or decompensation following left ventricular assist device implantation, MI, heart transplant, or open-heart surgery.
The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including PE.
The Impella RP is authorized only for emergency use under the EUA and only for the duration of the circumstances justifying use of EUAs, the letter noted.
Last year, concerns were raised about off-indication use after interim results from a postapproval study suggested a higher risk for death than seen in premarket studies treated with the temporary heart pump.
A version of this article originally appeared on Medscape.com.
DoD to Return to Work in Phases
The US Department of Defense (DoD) has unveiled a plan for returning to normal operations. The plan is tied to “local conditions” and does not have specific dates for opening. Instead, the plan provides phase-by-phase guidance to commanders, supervisors, and employees to safely and effectively return to Pentagon Reservation offices. Along with guidelines for in-office and telework targets; vulnerable populations; entrance screening; and the status and cleaning of common areas, food courts, gyms and other facilities, the plan includes mandatory requirements regarding face coverings, social distancing, and symptomatic personnel throughout each phase.
Building on the 3-phase White House “Opening Up America Again” plan, the Joint Staff, military services, and the DoD COVID Task Force have developed a 5-phase plan. Currently, the department is at Phase Zero. The Pentagon Reservation Plan for Resilience and ‘Aligning with National Guidelines for Opening Up America Again’ “places the health and safety of our workforce first,” is “nested” within the White House, Office of Management and Budget, and Office of Personnel Management guidelines and plans. The goal is to allow the workforce to return to the Pentagon Reservation “in a controlled and steady manner.”
The DoD reported nearly 10,000 COVID-19 cases as of June 1, 2020, including 6,596 active-duty service members, 1,124 dependents, 1,516 civilians, and 649 DoD contractors. To date, 3 service members and 5 dependents have died of COVID-19, including Capt. Douglas Linn Hickok, a physician assistant and member of the New Jersey National Guard, who died March 28, 2020.
Since mid-March the DoD says it has taken “aggressive steps” to stop the spread of COVID-19, implementing health protection measures that resulted in a sustained transmission rate below that of the region at large. Teams have deep cleaned and sanitized more than 1 million square feet of office space on the Pentagon Reservation to US Centers for Disease Control and Prevention standards. And for the first time ever, according to the DoD, maximized telework options have enabled more than two-thirds of the Pentagon Reservation workforce to continue to work at alternate locations.
The criteria to enter Phase 1 require a downward trajectory of influenza-like illnesses reported with a 14-day period and a downward trajectory of COVID-like symptoms reported within a 14-day period. There must also be a downward trajectory of documented COVID-19 cases within a 14-day period or a downward trajectory of positive COVID-19 tests as a percentage of total tests within a 14-day period (flat or increasing volume of tests).
Finally, hospitals must treat all patients without crisis care and have a “robust” testing program in place for at-risk health care workers, including emerging antibody testing.
Those same criteria must be met between each phase of the plan. The “gates” for controlling moves from phase to phase are not tied to dates but are based on state, regional, and local public health conditions, availability of hospitals and testing capacity, and monitoring through the DoD’s Electronic Surveillance System for Early Notification of Community-based Epidemics (ESSENCE).
If the monitors detect a resurgence in the spread of COVID-19, the department will reassess its protection measures and workforce phase and respond appropriately. DoD service members and civilian employees are advised to talk with their commanders or supervisors to determine when it’s all right to return.
The US Department of Defense (DoD) has unveiled a plan for returning to normal operations. The plan is tied to “local conditions” and does not have specific dates for opening. Instead, the plan provides phase-by-phase guidance to commanders, supervisors, and employees to safely and effectively return to Pentagon Reservation offices. Along with guidelines for in-office and telework targets; vulnerable populations; entrance screening; and the status and cleaning of common areas, food courts, gyms and other facilities, the plan includes mandatory requirements regarding face coverings, social distancing, and symptomatic personnel throughout each phase.
Building on the 3-phase White House “Opening Up America Again” plan, the Joint Staff, military services, and the DoD COVID Task Force have developed a 5-phase plan. Currently, the department is at Phase Zero. The Pentagon Reservation Plan for Resilience and ‘Aligning with National Guidelines for Opening Up America Again’ “places the health and safety of our workforce first,” is “nested” within the White House, Office of Management and Budget, and Office of Personnel Management guidelines and plans. The goal is to allow the workforce to return to the Pentagon Reservation “in a controlled and steady manner.”
The DoD reported nearly 10,000 COVID-19 cases as of June 1, 2020, including 6,596 active-duty service members, 1,124 dependents, 1,516 civilians, and 649 DoD contractors. To date, 3 service members and 5 dependents have died of COVID-19, including Capt. Douglas Linn Hickok, a physician assistant and member of the New Jersey National Guard, who died March 28, 2020.
Since mid-March the DoD says it has taken “aggressive steps” to stop the spread of COVID-19, implementing health protection measures that resulted in a sustained transmission rate below that of the region at large. Teams have deep cleaned and sanitized more than 1 million square feet of office space on the Pentagon Reservation to US Centers for Disease Control and Prevention standards. And for the first time ever, according to the DoD, maximized telework options have enabled more than two-thirds of the Pentagon Reservation workforce to continue to work at alternate locations.
The criteria to enter Phase 1 require a downward trajectory of influenza-like illnesses reported with a 14-day period and a downward trajectory of COVID-like symptoms reported within a 14-day period. There must also be a downward trajectory of documented COVID-19 cases within a 14-day period or a downward trajectory of positive COVID-19 tests as a percentage of total tests within a 14-day period (flat or increasing volume of tests).
Finally, hospitals must treat all patients without crisis care and have a “robust” testing program in place for at-risk health care workers, including emerging antibody testing.
Those same criteria must be met between each phase of the plan. The “gates” for controlling moves from phase to phase are not tied to dates but are based on state, regional, and local public health conditions, availability of hospitals and testing capacity, and monitoring through the DoD’s Electronic Surveillance System for Early Notification of Community-based Epidemics (ESSENCE).
If the monitors detect a resurgence in the spread of COVID-19, the department will reassess its protection measures and workforce phase and respond appropriately. DoD service members and civilian employees are advised to talk with their commanders or supervisors to determine when it’s all right to return.
The US Department of Defense (DoD) has unveiled a plan for returning to normal operations. The plan is tied to “local conditions” and does not have specific dates for opening. Instead, the plan provides phase-by-phase guidance to commanders, supervisors, and employees to safely and effectively return to Pentagon Reservation offices. Along with guidelines for in-office and telework targets; vulnerable populations; entrance screening; and the status and cleaning of common areas, food courts, gyms and other facilities, the plan includes mandatory requirements regarding face coverings, social distancing, and symptomatic personnel throughout each phase.
Building on the 3-phase White House “Opening Up America Again” plan, the Joint Staff, military services, and the DoD COVID Task Force have developed a 5-phase plan. Currently, the department is at Phase Zero. The Pentagon Reservation Plan for Resilience and ‘Aligning with National Guidelines for Opening Up America Again’ “places the health and safety of our workforce first,” is “nested” within the White House, Office of Management and Budget, and Office of Personnel Management guidelines and plans. The goal is to allow the workforce to return to the Pentagon Reservation “in a controlled and steady manner.”
The DoD reported nearly 10,000 COVID-19 cases as of June 1, 2020, including 6,596 active-duty service members, 1,124 dependents, 1,516 civilians, and 649 DoD contractors. To date, 3 service members and 5 dependents have died of COVID-19, including Capt. Douglas Linn Hickok, a physician assistant and member of the New Jersey National Guard, who died March 28, 2020.
Since mid-March the DoD says it has taken “aggressive steps” to stop the spread of COVID-19, implementing health protection measures that resulted in a sustained transmission rate below that of the region at large. Teams have deep cleaned and sanitized more than 1 million square feet of office space on the Pentagon Reservation to US Centers for Disease Control and Prevention standards. And for the first time ever, according to the DoD, maximized telework options have enabled more than two-thirds of the Pentagon Reservation workforce to continue to work at alternate locations.
The criteria to enter Phase 1 require a downward trajectory of influenza-like illnesses reported with a 14-day period and a downward trajectory of COVID-like symptoms reported within a 14-day period. There must also be a downward trajectory of documented COVID-19 cases within a 14-day period or a downward trajectory of positive COVID-19 tests as a percentage of total tests within a 14-day period (flat or increasing volume of tests).
Finally, hospitals must treat all patients without crisis care and have a “robust” testing program in place for at-risk health care workers, including emerging antibody testing.
Those same criteria must be met between each phase of the plan. The “gates” for controlling moves from phase to phase are not tied to dates but are based on state, regional, and local public health conditions, availability of hospitals and testing capacity, and monitoring through the DoD’s Electronic Surveillance System for Early Notification of Community-based Epidemics (ESSENCE).
If the monitors detect a resurgence in the spread of COVID-19, the department will reassess its protection measures and workforce phase and respond appropriately. DoD service members and civilian employees are advised to talk with their commanders or supervisors to determine when it’s all right to return.
Update: MS in Underserved Populations
As the United States population becomes increasingly diverse, the population of Americans living with neurological diseases such as multiple sclerosis (MS) will have more varied needs and greater health care inequities that may drive poorer outcomes.
In this supplement to Federal Practitioner, Victor M. Rivera, MD, FAAN, Mitzi Joi Williams, MD, and Patricia Pagnotta, ARNP-C, MSN, CNRN, MSCN discuss MS in minority populations such as African Americans, Hispanic Americans, and the military-veteran population. Topics include population-specific risk factors, disparities in clinical trial participation, and recommendations for improved MS management.
This supplement is sponsored by Biogen.
As the United States population becomes increasingly diverse, the population of Americans living with neurological diseases such as multiple sclerosis (MS) will have more varied needs and greater health care inequities that may drive poorer outcomes.
In this supplement to Federal Practitioner, Victor M. Rivera, MD, FAAN, Mitzi Joi Williams, MD, and Patricia Pagnotta, ARNP-C, MSN, CNRN, MSCN discuss MS in minority populations such as African Americans, Hispanic Americans, and the military-veteran population. Topics include population-specific risk factors, disparities in clinical trial participation, and recommendations for improved MS management.
This supplement is sponsored by Biogen.
As the United States population becomes increasingly diverse, the population of Americans living with neurological diseases such as multiple sclerosis (MS) will have more varied needs and greater health care inequities that may drive poorer outcomes.
In this supplement to Federal Practitioner, Victor M. Rivera, MD, FAAN, Mitzi Joi Williams, MD, and Patricia Pagnotta, ARNP-C, MSN, CNRN, MSCN discuss MS in minority populations such as African Americans, Hispanic Americans, and the military-veteran population. Topics include population-specific risk factors, disparities in clinical trial participation, and recommendations for improved MS management.
This supplement is sponsored by Biogen.
Research News: Neurologic Disorders (FULL)
Modest Evidence for Benefit in Studies of Cannabis in MS
While several dozen studies have been conducted into cannabis-based treatments for symptoms of multiple sclerosis (MS), a new systematic review deems most to be of fair to poor quality. Reviewers found modest evidence of benefit and plenty of room for more research.
“Cannabis-based medicine may be useful for refractory MS symptoms, especially spasticity and pain, and side effects are usually well tolerated,” study lead author Natasha Breward, a graduate student at the College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, said in an interview. Breward spoke prior to the presentation of the study findings at the 2019 meeting of the Consortium of Multiple Sclerosis Centers.
For the review, Breward and colleagues focused on 60 studies—26 randomized controlled trials and 34 trials with other designs. Forty of the studies used nabiximols, an oromucosal spray that is derived from the cannabis sativa plant and approved for use in multiple countries but not yet in the US.
According to Breward, some of the other treatments included dried cannabis that is smoked or eaten and cannabidiol that’s typically delivered with tetrahydrocannabinol (THC) either oromucosally or as an oral capsule.
MS symptoms treated in the studies included spasticity (n = 29), pain (n = 8), and cognition (n = 6). The researchers considered 22 studies to be poor quality, 14 to be fair quality, and 24 to be good/excellent quality.
The researchers found that the cannabis-based medicine “significantly reduced spasticity and pain in several individual good-quality studies,” Breward said. The drugs seem to work by inhibiting neurotransmitter release via cannabinoids. “However, the variability in study quality—and in the products and regimens studied—make it hard to draw any conclusions about specific products and doses that may have the most potential benefit,” she added.
“Further research should focus on the use of different products and formulations of cannabis-based medicine such as cannabis oil and cannabidiol-prominent products, as no studies have focused on this area,” she said. “Research should also look at the potential of cannabis-based medicine for the treatment of disease progression, as cannabinoids are anti-inflammatory and immunomodulatory. Finally, more research regarding the potentially synergistic effects of cannabis-based medicine administered with current MS medications would also be useful.”
Randy Dotinga, MDedge.com/neurology
Brain Volumes After TBI Correlate With Clinical Features
Brain volumes of specific regions of interest can be used to classify traumatic brain injury subjects that fall into predetermined symptom categories, according to a study presented at the annual meeting of the American Academy of Neurology.
Traumatic brain injury (TBI) damages brain tissue and causes subsequent volume loss, which may result in clinical symptoms. It is a prevalent worldwide health problem caused by a mechanical insult to the head, resulting in transient or permanent alteration to brain tissue and/or function. Standard neuroimaging with computed cranial tomography (CT) and structural magnetic resonance imaging (MRI) is often unrevealing during the evaluation of patients with TBI, particularly those classified as mild TBI.
In this study, James Rock, MD, of Penn Presbyterian Medical Center and the University of Pennsylvania, and colleagues sought to examine the value of quantitative analysis of regional brain volumes in the evaluation of TBI. The investigators reviewed the medical records and MRI imaging from 44 patients with TBI evaluated at a Level I trauma center. They also read clinical notes to assess reported symptoms and physical findings.
Regional volumes from TBI subjects were derived using the software package Freesurfer image analysis suite (surfer.nmr.mgh.harvard.edu), which utilizes a T1-weighted structural scan to calculate volumetric information. A machine learning algorithm, random forests, was employed across volume measurements from 25 regions of interest to determine the most important regions for classifying subjects based on clinical outcome and symptomology.
Basal ganglia volume showed the highest variable importance with regards to classifying subjects who exhibited symptoms of cognitive dysfunction in quantitative analysis. Left lateral ventricle volume was important in classifying subjects with motor and vestibular alterations. Left choroid plexus volume was the most important region for classifying subjects with sensation and somatic dysfunction.
In an abstract, the researchers noted that their study is ongoing. “It will be extended to a larger cohort to determine whether volume changes in specific [regions of interest] can act as useful clinical biomarkers for chronic symptoms,” they said.
Dr. Diaz-Arrastia received personal compensation from Neural Analytics, Inc; BrainBox Solutions, Inc; and Bioscience Pharma Partners. Dr. Diaz-Arrastia holds stock and/or stock options in Neural Analytics, Inc and has received research support from BrainBox Solutions. The other authors reported no other disclosures.
Glenn S. Williams, MDedge.com/neurology
What Other Drugs Do Patients Take When They Start MS Therapy?
Concomitant medication use is common when patients with multiple sclerosis (MS) start disease-modifying drugs (DMDs), according to research presented at the 2019 meeting of the Consortium of Multiple Sclerosis Centers. The likelihood of particular comorbidities and concomitant medications varies by age and sex, researchers reported.
“This may have implications for MS treatment,” said study author Jacqueline Nicholas, MD, MPH, of Ohio Multiple Sclerosis Center in Columbus and colleagues. “A better understanding of the effects of comorbidities and concomitant medications on the effectiveness and safety of DMDs is needed to support clinical decision making.”
Researchers have examined comorbidities in patients with MS, but concomitant medication use among patients starting DMDs is poorly understood, the authors said.
To study this question, Dr. Nicholas and colleagues analyzed retrospective administrative claims data from IQVIA Real-World Data Adjudicated Claims–US database from Jan. 1, 2010, to June 30, 2017. Their analysis included patients with ≥ 2 MS diagnosis claims and at least 1 DMD claim between Jan. 1, 2011, and June 30, 2015. Eligible patients were aged 18 to 63 years and had continuous eligibility with commercial insurance 1 year before and 2 years after DMD initiation. In addition, patients had no evidence of DMD use during the 1-year baseline period.
The investigators used International Classification of Diseases, 9th and 10th revisions, Clinical Modification codes and claims to evaluate patients’ comorbidities and concomitant medications during the study period.
The researchers identified 8,251 eligible patients. Patients had a mean age of 43.2 years, and 75.5% were female. Average baseline Charlson Comorbidity Index was 0.41. In the 2 years after DMD initiation, common comorbid diagnoses were hyperlipidemia (30.0%), hypertension (28.2%), gastrointestinal disorders (26.2%), depression (25.5%), and anxiety (20.1%).
Common concomitant medications included antibiotics (70.6%); analgesics (57.0%); corticosteroids (52.0%); antidepressants (47.7%); anticonvulsants (46.7%); anxiolytics, sedatives, or hypnotics (43.2%); spasticity medications (36.2%); and muscle relaxants (35.4%).
Most comorbidities and many medications, including bladder and antifatigue medications, were more common among patients aged ≥ 55 years. Hyperlipidemia, hypertension, and diabetes mellitus were more likely in males than in females. Females were more likely to have gastrointestinal disease, depression, thyroid disease, anxiety, lung disease, and arthritis. In addition, females were more likely than males to use many of the concomitant medications.
Dr. Nicholas disclosed grant support from EMD Serono. A coauthor is an employee of Health Services Consulting Corporation and received funding from EMD Serono to conduct the study. Other coauthors are employees of EMD Serono.
Jake Rem
Depression, Fatigue, Pain, and Anxiety Are Common in the Year After MS Diagnosis
In the 12 months after diagnosis, pain, fatigue, depression, and anxiety are common among patients with multiple sclerosis (MS), researchers reported at the 2019 meeting of the Consortium of Multiple Sclerosis Centers. In a novel study, about half of patients with MS reported clinically significant symptoms of depression or pain, and about 60% reported fatigue during that time.
Pain, fatigue, depression, and anxiety are common in MS, but their prevalence in the first year after diagnosis is not well understood. To examine the rates of these conditions and how often they co-occur during that period, Anna L. Kratz, PhD, associate professor of physical medicine and rehabilitation at the University of Michigan in Ann Arbor, and her research colleagues had 231 adults with MS complete validated surveys at 1, 2, 3, 6, 9, and 12 months after diagnosis to assess symptoms of these conditions.
Overall, 47.2% of patients reported clinically significant levels of depression, 38.5% reported clinically significant levels of anxiety, 50.4% reported clinically significant pain, and 62.2% reported clinically significant fatigue at any point during the year after diagnosis. “Of those who did not have clinically significant symptoms at time of diagnosis, 21.3% went on to develop clinically significant depression, 17.0% anxiety, 30.9% pain, and 34.1% fatigue,” the authors reported.
About 23% of patients did not have clinically significant symptoms for any condition, while 20% had clinically significant symptoms for 1 condition, 21% for 2, 19% for 3, and 17% for all 4. Depression and fatigue had the highest rate of comorbidity, whereas pain and anxiety had the lowest rate of comorbidity.
“Important clinical symptoms associated with MS are present at high levels in the first year post diagnosis,” Dr. Kratz and colleagues concluded. “While the rates and severity are marginally lower than have been identified in studies of individuals farther into the MS disease course, this study is a reminder that early MS intervention should incorporate interventions for these symptoms that are known to have strong associations with quality of life.”
The researchers had no disclosures.
Jake Remaly, MDedge.com/neurology
Experts Propose New Definition and Recommendations for Alzheimer-like Disorder
An international group of experts has proposed a new name, staging criteria, and recommendations for a recently recognized brain disorder that mimics Alzheimer disease and is marked by a proteinopathy caused by malformed transactive response DNA-binding protein of 43 kDa (TDP-43).
The term limbic-predominant age-related TDP-43 encephalopathy (LATE) was coined in an effort to raise awareness and kick-start research into this “pathway to dementia,” the experts wrote in a report appearing in Brain. “As there is currently no universally agreed-upon terminology or staging system for common age-related TDP-43 proteinopathy, this condition is understudied and not well recognized, even among investigators in the field of dementia research,” wrote the authors of the report, led by Peter T. Nelson, MD, PhD, of the University of Kentucky, Lexington.
LATE neuropathologic changes, associated with a progressive amnesia syndrome that mimics Alzheimer, are seen in > 20% of individuals aged > 80 years, according to large, community-based autopsy series. It coexists with Alzheimer disease in many patients, lowering the threshold for developing dementia, authors said.
The term LATE is designed to encompass several other terms related to TDP-43 pathology, including hippocampal sclerosis and cerebral age-related TDP-43 with sclerosis, Dr. Nelson and colleagues noted.
The TDP-43 protein is encoded by the TARDBP gene and provides several functions related to the regulation of gene expression, the authors wrote.
Misfolded TDP-43 was known to play a causative role in amyotrophic lateral sclerosis and frontotemporal lobar degeneration, the authors noted, and then was also identified in the brains of older individuals with hippocampal sclerosis or Alzheimer disease neuropathologic changes.
The authors proposed a 3-stage classification system for LATE neuropathologic change based on TDP-43 immunohistochemistry performed during routine autopsy evaluation of the amygdala, hippocampus, and middle frontal gyrus. The amygdala is an area affected early in the course of the disease (Stage 1), whereas involvement of the hippocampus represents a more intermediate stage (Stage 2), and the middle frontal gyrus is more affected in advanced stages of the disease (Stage 3), according to the schema.
Five genes have been identified with risk alleles for LATE neuropathologic changes, authors said. Of note, several groups have found that the apolipoprotein E ∑ 4 allele, known to be a risk factor for Alzheimer disease neuropathologic changes and Lewy body disease, is also linked to increased risk of TDP-43 proteinopathy.
There are no established biomarkers specific to TDP-43 proteinopathy yet, which hampers development of clinical trials designed to test interventions to treat or prevent LATE, Dr. Nelson and colleagues said in their report. LATE also could obscure the effects of potentially disease-modifying agents being tested in Alzheimer disease clinical trials, which can complicate the interpretation of study results, they added.
“Until there are biomarkers for LATE, clinical trials should be powered to account for TDP-43 proteinopathy,” they wrote. Dr. Nelson and coauthors reported no author disclosures.
Source: Nelson PT, Dickson DW, Trojanowski JQ, et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain. 2019;142(6):1503-1527.
Andrew D. Bowser, MDedge.com/neurology
Modest Evidence for Benefit in Studies of Cannabis in MS
While several dozen studies have been conducted into cannabis-based treatments for symptoms of multiple sclerosis (MS), a new systematic review deems most to be of fair to poor quality. Reviewers found modest evidence of benefit and plenty of room for more research.
“Cannabis-based medicine may be useful for refractory MS symptoms, especially spasticity and pain, and side effects are usually well tolerated,” study lead author Natasha Breward, a graduate student at the College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, said in an interview. Breward spoke prior to the presentation of the study findings at the 2019 meeting of the Consortium of Multiple Sclerosis Centers.
For the review, Breward and colleagues focused on 60 studies—26 randomized controlled trials and 34 trials with other designs. Forty of the studies used nabiximols, an oromucosal spray that is derived from the cannabis sativa plant and approved for use in multiple countries but not yet in the US.
According to Breward, some of the other treatments included dried cannabis that is smoked or eaten and cannabidiol that’s typically delivered with tetrahydrocannabinol (THC) either oromucosally or as an oral capsule.
MS symptoms treated in the studies included spasticity (n = 29), pain (n = 8), and cognition (n = 6). The researchers considered 22 studies to be poor quality, 14 to be fair quality, and 24 to be good/excellent quality.
The researchers found that the cannabis-based medicine “significantly reduced spasticity and pain in several individual good-quality studies,” Breward said. The drugs seem to work by inhibiting neurotransmitter release via cannabinoids. “However, the variability in study quality—and in the products and regimens studied—make it hard to draw any conclusions about specific products and doses that may have the most potential benefit,” she added.
“Further research should focus on the use of different products and formulations of cannabis-based medicine such as cannabis oil and cannabidiol-prominent products, as no studies have focused on this area,” she said. “Research should also look at the potential of cannabis-based medicine for the treatment of disease progression, as cannabinoids are anti-inflammatory and immunomodulatory. Finally, more research regarding the potentially synergistic effects of cannabis-based medicine administered with current MS medications would also be useful.”
Randy Dotinga, MDedge.com/neurology
Brain Volumes After TBI Correlate With Clinical Features
Brain volumes of specific regions of interest can be used to classify traumatic brain injury subjects that fall into predetermined symptom categories, according to a study presented at the annual meeting of the American Academy of Neurology.
Traumatic brain injury (TBI) damages brain tissue and causes subsequent volume loss, which may result in clinical symptoms. It is a prevalent worldwide health problem caused by a mechanical insult to the head, resulting in transient or permanent alteration to brain tissue and/or function. Standard neuroimaging with computed cranial tomography (CT) and structural magnetic resonance imaging (MRI) is often unrevealing during the evaluation of patients with TBI, particularly those classified as mild TBI.
In this study, James Rock, MD, of Penn Presbyterian Medical Center and the University of Pennsylvania, and colleagues sought to examine the value of quantitative analysis of regional brain volumes in the evaluation of TBI. The investigators reviewed the medical records and MRI imaging from 44 patients with TBI evaluated at a Level I trauma center. They also read clinical notes to assess reported symptoms and physical findings.
Regional volumes from TBI subjects were derived using the software package Freesurfer image analysis suite (surfer.nmr.mgh.harvard.edu), which utilizes a T1-weighted structural scan to calculate volumetric information. A machine learning algorithm, random forests, was employed across volume measurements from 25 regions of interest to determine the most important regions for classifying subjects based on clinical outcome and symptomology.
Basal ganglia volume showed the highest variable importance with regards to classifying subjects who exhibited symptoms of cognitive dysfunction in quantitative analysis. Left lateral ventricle volume was important in classifying subjects with motor and vestibular alterations. Left choroid plexus volume was the most important region for classifying subjects with sensation and somatic dysfunction.
In an abstract, the researchers noted that their study is ongoing. “It will be extended to a larger cohort to determine whether volume changes in specific [regions of interest] can act as useful clinical biomarkers for chronic symptoms,” they said.
Dr. Diaz-Arrastia received personal compensation from Neural Analytics, Inc; BrainBox Solutions, Inc; and Bioscience Pharma Partners. Dr. Diaz-Arrastia holds stock and/or stock options in Neural Analytics, Inc and has received research support from BrainBox Solutions. The other authors reported no other disclosures.
Glenn S. Williams, MDedge.com/neurology
What Other Drugs Do Patients Take When They Start MS Therapy?
Concomitant medication use is common when patients with multiple sclerosis (MS) start disease-modifying drugs (DMDs), according to research presented at the 2019 meeting of the Consortium of Multiple Sclerosis Centers. The likelihood of particular comorbidities and concomitant medications varies by age and sex, researchers reported.
“This may have implications for MS treatment,” said study author Jacqueline Nicholas, MD, MPH, of Ohio Multiple Sclerosis Center in Columbus and colleagues. “A better understanding of the effects of comorbidities and concomitant medications on the effectiveness and safety of DMDs is needed to support clinical decision making.”
Researchers have examined comorbidities in patients with MS, but concomitant medication use among patients starting DMDs is poorly understood, the authors said.
To study this question, Dr. Nicholas and colleagues analyzed retrospective administrative claims data from IQVIA Real-World Data Adjudicated Claims–US database from Jan. 1, 2010, to June 30, 2017. Their analysis included patients with ≥ 2 MS diagnosis claims and at least 1 DMD claim between Jan. 1, 2011, and June 30, 2015. Eligible patients were aged 18 to 63 years and had continuous eligibility with commercial insurance 1 year before and 2 years after DMD initiation. In addition, patients had no evidence of DMD use during the 1-year baseline period.
The investigators used International Classification of Diseases, 9th and 10th revisions, Clinical Modification codes and claims to evaluate patients’ comorbidities and concomitant medications during the study period.
The researchers identified 8,251 eligible patients. Patients had a mean age of 43.2 years, and 75.5% were female. Average baseline Charlson Comorbidity Index was 0.41. In the 2 years after DMD initiation, common comorbid diagnoses were hyperlipidemia (30.0%), hypertension (28.2%), gastrointestinal disorders (26.2%), depression (25.5%), and anxiety (20.1%).
Common concomitant medications included antibiotics (70.6%); analgesics (57.0%); corticosteroids (52.0%); antidepressants (47.7%); anticonvulsants (46.7%); anxiolytics, sedatives, or hypnotics (43.2%); spasticity medications (36.2%); and muscle relaxants (35.4%).
Most comorbidities and many medications, including bladder and antifatigue medications, were more common among patients aged ≥ 55 years. Hyperlipidemia, hypertension, and diabetes mellitus were more likely in males than in females. Females were more likely to have gastrointestinal disease, depression, thyroid disease, anxiety, lung disease, and arthritis. In addition, females were more likely than males to use many of the concomitant medications.
Dr. Nicholas disclosed grant support from EMD Serono. A coauthor is an employee of Health Services Consulting Corporation and received funding from EMD Serono to conduct the study. Other coauthors are employees of EMD Serono.
Jake Rem
Depression, Fatigue, Pain, and Anxiety Are Common in the Year After MS Diagnosis
In the 12 months after diagnosis, pain, fatigue, depression, and anxiety are common among patients with multiple sclerosis (MS), researchers reported at the 2019 meeting of the Consortium of Multiple Sclerosis Centers. In a novel study, about half of patients with MS reported clinically significant symptoms of depression or pain, and about 60% reported fatigue during that time.
Pain, fatigue, depression, and anxiety are common in MS, but their prevalence in the first year after diagnosis is not well understood. To examine the rates of these conditions and how often they co-occur during that period, Anna L. Kratz, PhD, associate professor of physical medicine and rehabilitation at the University of Michigan in Ann Arbor, and her research colleagues had 231 adults with MS complete validated surveys at 1, 2, 3, 6, 9, and 12 months after diagnosis to assess symptoms of these conditions.
Overall, 47.2% of patients reported clinically significant levels of depression, 38.5% reported clinically significant levels of anxiety, 50.4% reported clinically significant pain, and 62.2% reported clinically significant fatigue at any point during the year after diagnosis. “Of those who did not have clinically significant symptoms at time of diagnosis, 21.3% went on to develop clinically significant depression, 17.0% anxiety, 30.9% pain, and 34.1% fatigue,” the authors reported.
About 23% of patients did not have clinically significant symptoms for any condition, while 20% had clinically significant symptoms for 1 condition, 21% for 2, 19% for 3, and 17% for all 4. Depression and fatigue had the highest rate of comorbidity, whereas pain and anxiety had the lowest rate of comorbidity.
“Important clinical symptoms associated with MS are present at high levels in the first year post diagnosis,” Dr. Kratz and colleagues concluded. “While the rates and severity are marginally lower than have been identified in studies of individuals farther into the MS disease course, this study is a reminder that early MS intervention should incorporate interventions for these symptoms that are known to have strong associations with quality of life.”
The researchers had no disclosures.
Jake Remaly, MDedge.com/neurology
Experts Propose New Definition and Recommendations for Alzheimer-like Disorder
An international group of experts has proposed a new name, staging criteria, and recommendations for a recently recognized brain disorder that mimics Alzheimer disease and is marked by a proteinopathy caused by malformed transactive response DNA-binding protein of 43 kDa (TDP-43).
The term limbic-predominant age-related TDP-43 encephalopathy (LATE) was coined in an effort to raise awareness and kick-start research into this “pathway to dementia,” the experts wrote in a report appearing in Brain. “As there is currently no universally agreed-upon terminology or staging system for common age-related TDP-43 proteinopathy, this condition is understudied and not well recognized, even among investigators in the field of dementia research,” wrote the authors of the report, led by Peter T. Nelson, MD, PhD, of the University of Kentucky, Lexington.
LATE neuropathologic changes, associated with a progressive amnesia syndrome that mimics Alzheimer, are seen in > 20% of individuals aged > 80 years, according to large, community-based autopsy series. It coexists with Alzheimer disease in many patients, lowering the threshold for developing dementia, authors said.
The term LATE is designed to encompass several other terms related to TDP-43 pathology, including hippocampal sclerosis and cerebral age-related TDP-43 with sclerosis, Dr. Nelson and colleagues noted.
The TDP-43 protein is encoded by the TARDBP gene and provides several functions related to the regulation of gene expression, the authors wrote.
Misfolded TDP-43 was known to play a causative role in amyotrophic lateral sclerosis and frontotemporal lobar degeneration, the authors noted, and then was also identified in the brains of older individuals with hippocampal sclerosis or Alzheimer disease neuropathologic changes.
The authors proposed a 3-stage classification system for LATE neuropathologic change based on TDP-43 immunohistochemistry performed during routine autopsy evaluation of the amygdala, hippocampus, and middle frontal gyrus. The amygdala is an area affected early in the course of the disease (Stage 1), whereas involvement of the hippocampus represents a more intermediate stage (Stage 2), and the middle frontal gyrus is more affected in advanced stages of the disease (Stage 3), according to the schema.
Five genes have been identified with risk alleles for LATE neuropathologic changes, authors said. Of note, several groups have found that the apolipoprotein E ∑ 4 allele, known to be a risk factor for Alzheimer disease neuropathologic changes and Lewy body disease, is also linked to increased risk of TDP-43 proteinopathy.
There are no established biomarkers specific to TDP-43 proteinopathy yet, which hampers development of clinical trials designed to test interventions to treat or prevent LATE, Dr. Nelson and colleagues said in their report. LATE also could obscure the effects of potentially disease-modifying agents being tested in Alzheimer disease clinical trials, which can complicate the interpretation of study results, they added.
“Until there are biomarkers for LATE, clinical trials should be powered to account for TDP-43 proteinopathy,” they wrote. Dr. Nelson and coauthors reported no author disclosures.
Source: Nelson PT, Dickson DW, Trojanowski JQ, et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain. 2019;142(6):1503-1527.
Andrew D. Bowser, MDedge.com/neurology
Modest Evidence for Benefit in Studies of Cannabis in MS
While several dozen studies have been conducted into cannabis-based treatments for symptoms of multiple sclerosis (MS), a new systematic review deems most to be of fair to poor quality. Reviewers found modest evidence of benefit and plenty of room for more research.
“Cannabis-based medicine may be useful for refractory MS symptoms, especially spasticity and pain, and side effects are usually well tolerated,” study lead author Natasha Breward, a graduate student at the College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, said in an interview. Breward spoke prior to the presentation of the study findings at the 2019 meeting of the Consortium of Multiple Sclerosis Centers.
For the review, Breward and colleagues focused on 60 studies—26 randomized controlled trials and 34 trials with other designs. Forty of the studies used nabiximols, an oromucosal spray that is derived from the cannabis sativa plant and approved for use in multiple countries but not yet in the US.
According to Breward, some of the other treatments included dried cannabis that is smoked or eaten and cannabidiol that’s typically delivered with tetrahydrocannabinol (THC) either oromucosally or as an oral capsule.
MS symptoms treated in the studies included spasticity (n = 29), pain (n = 8), and cognition (n = 6). The researchers considered 22 studies to be poor quality, 14 to be fair quality, and 24 to be good/excellent quality.
The researchers found that the cannabis-based medicine “significantly reduced spasticity and pain in several individual good-quality studies,” Breward said. The drugs seem to work by inhibiting neurotransmitter release via cannabinoids. “However, the variability in study quality—and in the products and regimens studied—make it hard to draw any conclusions about specific products and doses that may have the most potential benefit,” she added.
“Further research should focus on the use of different products and formulations of cannabis-based medicine such as cannabis oil and cannabidiol-prominent products, as no studies have focused on this area,” she said. “Research should also look at the potential of cannabis-based medicine for the treatment of disease progression, as cannabinoids are anti-inflammatory and immunomodulatory. Finally, more research regarding the potentially synergistic effects of cannabis-based medicine administered with current MS medications would also be useful.”
Randy Dotinga, MDedge.com/neurology
Brain Volumes After TBI Correlate With Clinical Features
Brain volumes of specific regions of interest can be used to classify traumatic brain injury subjects that fall into predetermined symptom categories, according to a study presented at the annual meeting of the American Academy of Neurology.
Traumatic brain injury (TBI) damages brain tissue and causes subsequent volume loss, which may result in clinical symptoms. It is a prevalent worldwide health problem caused by a mechanical insult to the head, resulting in transient or permanent alteration to brain tissue and/or function. Standard neuroimaging with computed cranial tomography (CT) and structural magnetic resonance imaging (MRI) is often unrevealing during the evaluation of patients with TBI, particularly those classified as mild TBI.
In this study, James Rock, MD, of Penn Presbyterian Medical Center and the University of Pennsylvania, and colleagues sought to examine the value of quantitative analysis of regional brain volumes in the evaluation of TBI. The investigators reviewed the medical records and MRI imaging from 44 patients with TBI evaluated at a Level I trauma center. They also read clinical notes to assess reported symptoms and physical findings.
Regional volumes from TBI subjects were derived using the software package Freesurfer image analysis suite (surfer.nmr.mgh.harvard.edu), which utilizes a T1-weighted structural scan to calculate volumetric information. A machine learning algorithm, random forests, was employed across volume measurements from 25 regions of interest to determine the most important regions for classifying subjects based on clinical outcome and symptomology.
Basal ganglia volume showed the highest variable importance with regards to classifying subjects who exhibited symptoms of cognitive dysfunction in quantitative analysis. Left lateral ventricle volume was important in classifying subjects with motor and vestibular alterations. Left choroid plexus volume was the most important region for classifying subjects with sensation and somatic dysfunction.
In an abstract, the researchers noted that their study is ongoing. “It will be extended to a larger cohort to determine whether volume changes in specific [regions of interest] can act as useful clinical biomarkers for chronic symptoms,” they said.
Dr. Diaz-Arrastia received personal compensation from Neural Analytics, Inc; BrainBox Solutions, Inc; and Bioscience Pharma Partners. Dr. Diaz-Arrastia holds stock and/or stock options in Neural Analytics, Inc and has received research support from BrainBox Solutions. The other authors reported no other disclosures.
Glenn S. Williams, MDedge.com/neurology
What Other Drugs Do Patients Take When They Start MS Therapy?
Concomitant medication use is common when patients with multiple sclerosis (MS) start disease-modifying drugs (DMDs), according to research presented at the 2019 meeting of the Consortium of Multiple Sclerosis Centers. The likelihood of particular comorbidities and concomitant medications varies by age and sex, researchers reported.
“This may have implications for MS treatment,” said study author Jacqueline Nicholas, MD, MPH, of Ohio Multiple Sclerosis Center in Columbus and colleagues. “A better understanding of the effects of comorbidities and concomitant medications on the effectiveness and safety of DMDs is needed to support clinical decision making.”
Researchers have examined comorbidities in patients with MS, but concomitant medication use among patients starting DMDs is poorly understood, the authors said.
To study this question, Dr. Nicholas and colleagues analyzed retrospective administrative claims data from IQVIA Real-World Data Adjudicated Claims–US database from Jan. 1, 2010, to June 30, 2017. Their analysis included patients with ≥ 2 MS diagnosis claims and at least 1 DMD claim between Jan. 1, 2011, and June 30, 2015. Eligible patients were aged 18 to 63 years and had continuous eligibility with commercial insurance 1 year before and 2 years after DMD initiation. In addition, patients had no evidence of DMD use during the 1-year baseline period.
The investigators used International Classification of Diseases, 9th and 10th revisions, Clinical Modification codes and claims to evaluate patients’ comorbidities and concomitant medications during the study period.
The researchers identified 8,251 eligible patients. Patients had a mean age of 43.2 years, and 75.5% were female. Average baseline Charlson Comorbidity Index was 0.41. In the 2 years after DMD initiation, common comorbid diagnoses were hyperlipidemia (30.0%), hypertension (28.2%), gastrointestinal disorders (26.2%), depression (25.5%), and anxiety (20.1%).
Common concomitant medications included antibiotics (70.6%); analgesics (57.0%); corticosteroids (52.0%); antidepressants (47.7%); anticonvulsants (46.7%); anxiolytics, sedatives, or hypnotics (43.2%); spasticity medications (36.2%); and muscle relaxants (35.4%).
Most comorbidities and many medications, including bladder and antifatigue medications, were more common among patients aged ≥ 55 years. Hyperlipidemia, hypertension, and diabetes mellitus were more likely in males than in females. Females were more likely to have gastrointestinal disease, depression, thyroid disease, anxiety, lung disease, and arthritis. In addition, females were more likely than males to use many of the concomitant medications.
Dr. Nicholas disclosed grant support from EMD Serono. A coauthor is an employee of Health Services Consulting Corporation and received funding from EMD Serono to conduct the study. Other coauthors are employees of EMD Serono.
Jake Rem
Depression, Fatigue, Pain, and Anxiety Are Common in the Year After MS Diagnosis
In the 12 months after diagnosis, pain, fatigue, depression, and anxiety are common among patients with multiple sclerosis (MS), researchers reported at the 2019 meeting of the Consortium of Multiple Sclerosis Centers. In a novel study, about half of patients with MS reported clinically significant symptoms of depression or pain, and about 60% reported fatigue during that time.
Pain, fatigue, depression, and anxiety are common in MS, but their prevalence in the first year after diagnosis is not well understood. To examine the rates of these conditions and how often they co-occur during that period, Anna L. Kratz, PhD, associate professor of physical medicine and rehabilitation at the University of Michigan in Ann Arbor, and her research colleagues had 231 adults with MS complete validated surveys at 1, 2, 3, 6, 9, and 12 months after diagnosis to assess symptoms of these conditions.
Overall, 47.2% of patients reported clinically significant levels of depression, 38.5% reported clinically significant levels of anxiety, 50.4% reported clinically significant pain, and 62.2% reported clinically significant fatigue at any point during the year after diagnosis. “Of those who did not have clinically significant symptoms at time of diagnosis, 21.3% went on to develop clinically significant depression, 17.0% anxiety, 30.9% pain, and 34.1% fatigue,” the authors reported.
About 23% of patients did not have clinically significant symptoms for any condition, while 20% had clinically significant symptoms for 1 condition, 21% for 2, 19% for 3, and 17% for all 4. Depression and fatigue had the highest rate of comorbidity, whereas pain and anxiety had the lowest rate of comorbidity.
“Important clinical symptoms associated with MS are present at high levels in the first year post diagnosis,” Dr. Kratz and colleagues concluded. “While the rates and severity are marginally lower than have been identified in studies of individuals farther into the MS disease course, this study is a reminder that early MS intervention should incorporate interventions for these symptoms that are known to have strong associations with quality of life.”
The researchers had no disclosures.
Jake Remaly, MDedge.com/neurology
Experts Propose New Definition and Recommendations for Alzheimer-like Disorder
An international group of experts has proposed a new name, staging criteria, and recommendations for a recently recognized brain disorder that mimics Alzheimer disease and is marked by a proteinopathy caused by malformed transactive response DNA-binding protein of 43 kDa (TDP-43).
The term limbic-predominant age-related TDP-43 encephalopathy (LATE) was coined in an effort to raise awareness and kick-start research into this “pathway to dementia,” the experts wrote in a report appearing in Brain. “As there is currently no universally agreed-upon terminology or staging system for common age-related TDP-43 proteinopathy, this condition is understudied and not well recognized, even among investigators in the field of dementia research,” wrote the authors of the report, led by Peter T. Nelson, MD, PhD, of the University of Kentucky, Lexington.
LATE neuropathologic changes, associated with a progressive amnesia syndrome that mimics Alzheimer, are seen in > 20% of individuals aged > 80 years, according to large, community-based autopsy series. It coexists with Alzheimer disease in many patients, lowering the threshold for developing dementia, authors said.
The term LATE is designed to encompass several other terms related to TDP-43 pathology, including hippocampal sclerosis and cerebral age-related TDP-43 with sclerosis, Dr. Nelson and colleagues noted.
The TDP-43 protein is encoded by the TARDBP gene and provides several functions related to the regulation of gene expression, the authors wrote.
Misfolded TDP-43 was known to play a causative role in amyotrophic lateral sclerosis and frontotemporal lobar degeneration, the authors noted, and then was also identified in the brains of older individuals with hippocampal sclerosis or Alzheimer disease neuropathologic changes.
The authors proposed a 3-stage classification system for LATE neuropathologic change based on TDP-43 immunohistochemistry performed during routine autopsy evaluation of the amygdala, hippocampus, and middle frontal gyrus. The amygdala is an area affected early in the course of the disease (Stage 1), whereas involvement of the hippocampus represents a more intermediate stage (Stage 2), and the middle frontal gyrus is more affected in advanced stages of the disease (Stage 3), according to the schema.
Five genes have been identified with risk alleles for LATE neuropathologic changes, authors said. Of note, several groups have found that the apolipoprotein E ∑ 4 allele, known to be a risk factor for Alzheimer disease neuropathologic changes and Lewy body disease, is also linked to increased risk of TDP-43 proteinopathy.
There are no established biomarkers specific to TDP-43 proteinopathy yet, which hampers development of clinical trials designed to test interventions to treat or prevent LATE, Dr. Nelson and colleagues said in their report. LATE also could obscure the effects of potentially disease-modifying agents being tested in Alzheimer disease clinical trials, which can complicate the interpretation of study results, they added.
“Until there are biomarkers for LATE, clinical trials should be powered to account for TDP-43 proteinopathy,” they wrote. Dr. Nelson and coauthors reported no author disclosures.
Source: Nelson PT, Dickson DW, Trojanowski JQ, et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain. 2019;142(6):1503-1527.
Andrew D. Bowser, MDedge.com/neurology
Proton Pump Inhibitor Use and Risk of Dementia in the Veteran Population (FULL)
Proton pump inhibitors (PPIs) have become the mainstay of therapy in the treatment of acid-related disorders since their introduction in 1989. Due to their high potency, excellent tolerability, and generic availability, PPIs have largely replaced histamine-2 receptor antagonists for gastric problems. Since they were first released on the market, the use of PPIs has continued to rise in both the hospital and primary care settings.1 However, this rapid growth has led to the concern of overutilization. A study conducted at the Department of Veterans Affairs (VA) Ann Arbor Health Care System found that out of 946 patients in the ambulatory care setting taking PPIs, only 35% were appropriately prescribed PPIs.2
Although the short-term adverse effects of PPI use seem minimal, chronic PPI use consequences are a growing concern. Chronic PPI use is associated with increased risks of osteoporosis, pneumonia, and Clostridium difficile infections.3 Another long-term risk that has been associated with chronic PPI use is dementia. Dementia is a cognitive syndrome that is characterized by a progressive decline beyond what is expected in normal aging in 1 or more of the cognitive domains of memory, language, orientation, learning capacity, executive function, or social cognition.4 Because it interferes with activities of daily living, dementia is a major cause of disability in the elderly and is an immense burden for caregivers. Currently, about 47 million people globally live with dementia.5 This number is projected to nearly triple by 2050 to 132 million.5 With no cure, identification of risk factors and creation of protective measures are critical in decreasing the prevalence of dementia.
Although the exact pathophysiology behind the link between PPIs and dementia is unknown, several theories exist. One such theory is that PPI-induced vitamin B12 deficiency leads to cognitive decline.6,7 Another theory suggests that PPIs can directly cause dementia by inhibiting enzymes that normally degrade β amyloid.8 This leads to increased levels of β-amyloid plaques, which is a known characteristic of dementia patients. This theory is derived from animal studies that have shown increased amyloid levels in the brains of mice given PPIs.8
Current studies are conflicting regarding the association between PPIs and dementia. Two German prospective, cohort studies found statistically significant increased risks of dementia in patients taking PPIs with hazard ratios (HR) of 1.38 (95% CI, 1.04-1.83) and 1.44 (95% CI, 1.36-1.52), respectively.9,10 A study conducted in Taiwan also found an increased risk of dementia among PPI users with a HR of 1.22 (95% CI, 1.05-1.42).11 On the contrary, other studies have failed to show an increased risk of dementia with PPI use. In fact, Goldstein and colleagues found a decreased risk of dementia in PPI users with a HR of 0.78 (95% CI, 0.76-0.93).12 This study was an observational study conducted in the US using data from the National Alzheimer’s Coordinating Center database.12 Another recent retrospective study conducted in Finland showed that PPI use was not associated with a significantly increased risk of Alzheimer disease.13
Much is unknown about the cause of dementia, and no curative treatment exists. Investigation into potential risk factors for dementia can lead to the development of preventative measures, which can lead to significant improvement in quality of life for both patients and caregivers. Current studies regarding the association between PPIs and dementia are conflicting, and to our knowledge, no study analyzing the effects of PPIs and dementia has been conducted within the veteran population specifically. The objective of the current study is to investigate the association between PPI use and dementia in the veteran population.
Methods
This study is a retrospective, cohort, single-center, chart review study conducted at the Sioux Falls Veteran Affairs Health Care System (SFVAHCS). Data were extracted from the VA electronic health record (EHR) from January 1, 2005 through December 31, 2015. The study included both currently living and deceased veterans who received ≥ 2 documented outpatient visits at the SFVAHCS during the study time frame. Patients also had to be aged ≥ 60 years at the start of the study period. Patients were excluded if they received only a ≤ 30-day PPI prescription. Patients with dementia related to head trauma, acute intoxication, or other known diseases were excluded.
To analyze the primary endpoint of association between PPI use and dementia, the study compared the rate of dementia in a cohort of veterans who had received an outpatient prescription for a PPI within the study time frame vs the rate of dementia in a random, equal number of veterans who had never been prescribed PPIs within the study time frame. In this study, veterans were classified as having dementia if they had a diagnosis of dementia based on ICD-9 or ICD-10 codes (Table 1), or if they had been prescribed medications used to treat dementia (donepezil, ergoloid mesylates, galantamine, memantine, and rivastigmine).
Secondary endpoints included analysis of the effects of PPI agent, PPI dose, and PPI duration on the risk of dementia. For the PPI dose analysis, cumulative doses were converted into defined daily doses (DDDs) using the World Health Organization calculation to equalize the different potencies of PPI agents (Table 2).14 In addition, the effect of PPI use on vitamin B12 levels was analyzed as an exploratory endpoint to investigate the hypothesis that PPI may be associated with vitamin B12 deficiency, which in turn may be associated with dementia.6,7
Baseline characteristics were collected to determine the variability between the treatment and control group. Data collected included age, gender, past medical history of diseases that may increase risk of dementia, and anticholinergic drug use. Anticholinergic drugs were included if they were classified as having “definite anticholinergic effects” based on the Aging Brain Care Anticholinergic Burden Scale (Appendix).15
Statistical Analysis
The primary endpoint was analyzed using a χ2 for association test. For the secondary endpoints, a χ2 for association test was used for endpoints with nominal data, and the Mood median test was used for endpoints with continuous data. The exploratory endpoint analyzing vitamin B12 levels was analyzed with the Mood median test. A P value of < .05 was defined as being statistically significant. Power analysis was not performed since all veterans who met the criteria were included in the study.
Results
Records of 23,656 veterans were included in the study with 11,828 veterans in both the PPI cohort and the non-PPI cohort (Table 3).
Primary Endpoint
Within the PPI group, 1,119 (9.5%) veterans had dementia compared with only 740 (6.3%) veterans in the non-PPI group. There was a statistically significant association between PPI use and dementia (P < .001). These results yielded an odds ratio of 1.55 for dementia risk in PPI users vs nonusers and a relative risk increase of 51.4% for dementia risk with PPI use compared with no PPI use.
Secondary Endpoints
Users of rabeprazole had the highest rate of dementia (12.8%), followed by lansoprazole (10.9%), omeprazole (9.7%), esomeprazole (7.7%), and pantoprazole (7.0%). The rate of dementia for non-PPI users was 6.3% (P < .001). The median cumulative doses of PPIs were not significant: 597 DDDs (95% CI, 540-630) in the dementia group vs 570 DDDs (95% CI, 540-624) in the nondementia group (P = .79). The median cumulative duration of PPI use in the dementia group was 4.6 years (95% CI, 4.25-4.92) vs 5.3 years (95% CI, 5.08-5.42) in the nondementia group (P < .001).
Exploratory Endpoint
The median B12 level in the PPI group was 521 pg/mL (95% CI, 509-533) compared with 480 pg/mL (95% CI, 465-496) in the non-PPI group (P < .001). However, both groups fell within the normal range for vitamin B12 (200-900 pg/mL).16
Discussion
The aim of this study was to determine whether an association existed between PPI use and dementia. This study showed a statistically significant association between PPI use and dementia within the veteran population. This study also showed a significant association between specific PPI agents and dementia. When analyzing the individual PPI agents, the rabeprazole group yielded the strongest relationship. However, this study was not powered to evaluate and compare risks of dementia between individual PPI agents. More data are needed to determine statistical and clinical significance of associations between individual PPI agents and risk of dementia.
The veterans with dementia had a higher median cumulative PPI dose than did the veterans without dementia; however, the results were not statistically significant. Therefore, the data cannot correlate higher doses of PPI use to increased risk of dementia.
The cumulative duration of PPI use was statistically significant but opposite of the expected outcome. The dementia group had a lower median lifetime duration of PPI use compared with that of the nondementia group. It is difficult to determine the reason for this outcome, but it seems that for this study population, a longer duration of PPI use was not associated with an increased risk of dementia.
Finally, the exploratory endpoint analyzed vitamin B12 levels, since it has been shown that PPI use can lead to vitamin B12 deficiency and that B12 deficiency can lead to dementia.6-8 This study found that the dementia group had significantly higher vitamin B12 levels than the nondementia group. These data suggest that PPI use may not be associated with vitamin B12 deficiency. However, it is important to note that this study was unable to collect data on the use of vitamin B12 supplementation due to the unreliability of over-the-counter (OTC) and non-VA medication use records. Therefore, it is possible that the PPI group had higher rates of B12 deficiency but were effectively treated with B12 supplementation. More research is needed to determine the exact relationship between PPI use, vitamin B12 deficiency, and dementia risk.
Strengths/Limitations
Strengths of this study that support its findings include the large population size. Additionally, the use of the VA EHR allowed for a complete drug dispensing history to be collected, which improves reliability of the data.
This study also had some limitations. First, the causal relationship of PPI use and dementia cannot be proven using a retrospective cohort design. This study’s design can show association, but it cannot prove causation. Also, due to the retrospective design, exposure to PPI use could not be randomized; thus, correlation between PPI use and dementia may be explained by confounding variables that are not captured within this study. This is especially true since the baseline characteristics were not equally distributed between the 2 groups. In fact, the PPI group had higher rates of many clinical comorbidities. This imbalance may have skewed the results of the primary endpoint. Lastly, OTC PPI use and non-VA PPI prescriptions were not available. Therefore, some of the patients included in the non-PPI group may have been PPI users if they received PPIs from OTC or non-VA sources, which could skew the results.
Conclusion
This study showed a significant association between PPI use and dementia within the veteran study population. The study also showed a significant association between PPI use and dementia within the secondary endpoint of individual PPI agent. Higher cumulative dose and duration of PPI use did not seem to increase risk of dementia. Finally, PPI use was not associated with significantly low vitamin B12 levels. More studies are needed to determine causation of dementia and its risk factors.
Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Sioux Falls VA Health Care System.
1. Savarino V, Dulbecco P, de Bortoli N, Ottonello A, Savarino E. The appropriate use of proton pump inhibitors (PPIs): need for a reappraisal. Eur J Intern Med. 2017;37:19-24.
2. Heidelbaugh J, Goldberg K, Inadomi J. Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting. Am J Manag Care. 2010;16(9):e228-e234.
3. Heidelbaugh JJ, Kim AH, Chang R. Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5(4):219-232.
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, (DSM-5). American Psychiatric Association: Washington, DC; 2013.
5. World Health Organization. Dementia. http://www.who.int/mediacentre/factsheets/fs362/en/. Published December 12, 2017. Accessed March 10, 2019.
6. Vogiatzoglou A, Smith AD, Nurk E, et al. Cognitive function in an elderly population: interaction between vitamin B12 status, depression, and apolipoprotein E ε4: the Hordaland Homocysteine Study. Psychosom Med. 2013;75(1):20-29.
7. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442.
8. Badiola N, Alcalde V, Pujol A, et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013;8(3):e58837.
9. Haenisch B, von Holt K, Wiese B, et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci. 2015;265(5):419-428.
10. Gomm W, von Holt K, Thomé F, et al. Association between proton pump inhibitors with risk of dementia. A pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410-416.
11. Tai SY, Chien CY, Wu DC, et al. Risk of dementia from proton pump inhibitor use in Asian population: a nationwide cohort study in Taiwan. PLoS One. 2017;12(2):e0171006.
12. Goldstein FC, Steenland K, Zhao L, Wharton W, Levey AI, Hajjar I. Proton pump inhibitors and risk of mild cognitive impairment and dementia. J Am Geriatr Soc. 2017;65(9):1969-1674.
13. Taipale H, Tolppanen AM, Tiihonen M. Tanskanen A, Tiihonen J, Hartikainen S. No association between proton pump inhibitor use and risk of Alzheimer’s disease. Am J Gastroenterol. 2017;112(12):1801-1808.
14. World Health Organization Collaborating Centre for Drug Statistics Methodology. Definition and general considerations. https://www.whocc.no/ddd/definition_and_general_considera/. Updated February 7, 2018. Accessed March 13, 2019.
15. Indiana University Center for Aging Research, Aging Brain Program. Anticholinergic cognitive burden scale. http://www.idhca.org/wp-content/uploads/2018/02/DESAI_ACB_scale_-_Legal_size_paper.pdf. Updated 2012. Accessed March 10, 2019.
16. US National Library of Medicine, MedlinePlus. Vitamin B12 level. https://medlineplus.gov/ency/article/003705.htm. Updated March 7, 2019. Accessed March 13, 2019.
Proton pump inhibitors (PPIs) have become the mainstay of therapy in the treatment of acid-related disorders since their introduction in 1989. Due to their high potency, excellent tolerability, and generic availability, PPIs have largely replaced histamine-2 receptor antagonists for gastric problems. Since they were first released on the market, the use of PPIs has continued to rise in both the hospital and primary care settings.1 However, this rapid growth has led to the concern of overutilization. A study conducted at the Department of Veterans Affairs (VA) Ann Arbor Health Care System found that out of 946 patients in the ambulatory care setting taking PPIs, only 35% were appropriately prescribed PPIs.2
Although the short-term adverse effects of PPI use seem minimal, chronic PPI use consequences are a growing concern. Chronic PPI use is associated with increased risks of osteoporosis, pneumonia, and Clostridium difficile infections.3 Another long-term risk that has been associated with chronic PPI use is dementia. Dementia is a cognitive syndrome that is characterized by a progressive decline beyond what is expected in normal aging in 1 or more of the cognitive domains of memory, language, orientation, learning capacity, executive function, or social cognition.4 Because it interferes with activities of daily living, dementia is a major cause of disability in the elderly and is an immense burden for caregivers. Currently, about 47 million people globally live with dementia.5 This number is projected to nearly triple by 2050 to 132 million.5 With no cure, identification of risk factors and creation of protective measures are critical in decreasing the prevalence of dementia.
Although the exact pathophysiology behind the link between PPIs and dementia is unknown, several theories exist. One such theory is that PPI-induced vitamin B12 deficiency leads to cognitive decline.6,7 Another theory suggests that PPIs can directly cause dementia by inhibiting enzymes that normally degrade β amyloid.8 This leads to increased levels of β-amyloid plaques, which is a known characteristic of dementia patients. This theory is derived from animal studies that have shown increased amyloid levels in the brains of mice given PPIs.8
Current studies are conflicting regarding the association between PPIs and dementia. Two German prospective, cohort studies found statistically significant increased risks of dementia in patients taking PPIs with hazard ratios (HR) of 1.38 (95% CI, 1.04-1.83) and 1.44 (95% CI, 1.36-1.52), respectively.9,10 A study conducted in Taiwan also found an increased risk of dementia among PPI users with a HR of 1.22 (95% CI, 1.05-1.42).11 On the contrary, other studies have failed to show an increased risk of dementia with PPI use. In fact, Goldstein and colleagues found a decreased risk of dementia in PPI users with a HR of 0.78 (95% CI, 0.76-0.93).12 This study was an observational study conducted in the US using data from the National Alzheimer’s Coordinating Center database.12 Another recent retrospective study conducted in Finland showed that PPI use was not associated with a significantly increased risk of Alzheimer disease.13
Much is unknown about the cause of dementia, and no curative treatment exists. Investigation into potential risk factors for dementia can lead to the development of preventative measures, which can lead to significant improvement in quality of life for both patients and caregivers. Current studies regarding the association between PPIs and dementia are conflicting, and to our knowledge, no study analyzing the effects of PPIs and dementia has been conducted within the veteran population specifically. The objective of the current study is to investigate the association between PPI use and dementia in the veteran population.
Methods
This study is a retrospective, cohort, single-center, chart review study conducted at the Sioux Falls Veteran Affairs Health Care System (SFVAHCS). Data were extracted from the VA electronic health record (EHR) from January 1, 2005 through December 31, 2015. The study included both currently living and deceased veterans who received ≥ 2 documented outpatient visits at the SFVAHCS during the study time frame. Patients also had to be aged ≥ 60 years at the start of the study period. Patients were excluded if they received only a ≤ 30-day PPI prescription. Patients with dementia related to head trauma, acute intoxication, or other known diseases were excluded.
To analyze the primary endpoint of association between PPI use and dementia, the study compared the rate of dementia in a cohort of veterans who had received an outpatient prescription for a PPI within the study time frame vs the rate of dementia in a random, equal number of veterans who had never been prescribed PPIs within the study time frame. In this study, veterans were classified as having dementia if they had a diagnosis of dementia based on ICD-9 or ICD-10 codes (Table 1), or if they had been prescribed medications used to treat dementia (donepezil, ergoloid mesylates, galantamine, memantine, and rivastigmine).
Secondary endpoints included analysis of the effects of PPI agent, PPI dose, and PPI duration on the risk of dementia. For the PPI dose analysis, cumulative doses were converted into defined daily doses (DDDs) using the World Health Organization calculation to equalize the different potencies of PPI agents (Table 2).14 In addition, the effect of PPI use on vitamin B12 levels was analyzed as an exploratory endpoint to investigate the hypothesis that PPI may be associated with vitamin B12 deficiency, which in turn may be associated with dementia.6,7
Baseline characteristics were collected to determine the variability between the treatment and control group. Data collected included age, gender, past medical history of diseases that may increase risk of dementia, and anticholinergic drug use. Anticholinergic drugs were included if they were classified as having “definite anticholinergic effects” based on the Aging Brain Care Anticholinergic Burden Scale (Appendix).15
Statistical Analysis
The primary endpoint was analyzed using a χ2 for association test. For the secondary endpoints, a χ2 for association test was used for endpoints with nominal data, and the Mood median test was used for endpoints with continuous data. The exploratory endpoint analyzing vitamin B12 levels was analyzed with the Mood median test. A P value of < .05 was defined as being statistically significant. Power analysis was not performed since all veterans who met the criteria were included in the study.
Results
Records of 23,656 veterans were included in the study with 11,828 veterans in both the PPI cohort and the non-PPI cohort (Table 3).
Primary Endpoint
Within the PPI group, 1,119 (9.5%) veterans had dementia compared with only 740 (6.3%) veterans in the non-PPI group. There was a statistically significant association between PPI use and dementia (P < .001). These results yielded an odds ratio of 1.55 for dementia risk in PPI users vs nonusers and a relative risk increase of 51.4% for dementia risk with PPI use compared with no PPI use.
Secondary Endpoints
Users of rabeprazole had the highest rate of dementia (12.8%), followed by lansoprazole (10.9%), omeprazole (9.7%), esomeprazole (7.7%), and pantoprazole (7.0%). The rate of dementia for non-PPI users was 6.3% (P < .001). The median cumulative doses of PPIs were not significant: 597 DDDs (95% CI, 540-630) in the dementia group vs 570 DDDs (95% CI, 540-624) in the nondementia group (P = .79). The median cumulative duration of PPI use in the dementia group was 4.6 years (95% CI, 4.25-4.92) vs 5.3 years (95% CI, 5.08-5.42) in the nondementia group (P < .001).
Exploratory Endpoint
The median B12 level in the PPI group was 521 pg/mL (95% CI, 509-533) compared with 480 pg/mL (95% CI, 465-496) in the non-PPI group (P < .001). However, both groups fell within the normal range for vitamin B12 (200-900 pg/mL).16
Discussion
The aim of this study was to determine whether an association existed between PPI use and dementia. This study showed a statistically significant association between PPI use and dementia within the veteran population. This study also showed a significant association between specific PPI agents and dementia. When analyzing the individual PPI agents, the rabeprazole group yielded the strongest relationship. However, this study was not powered to evaluate and compare risks of dementia between individual PPI agents. More data are needed to determine statistical and clinical significance of associations between individual PPI agents and risk of dementia.
The veterans with dementia had a higher median cumulative PPI dose than did the veterans without dementia; however, the results were not statistically significant. Therefore, the data cannot correlate higher doses of PPI use to increased risk of dementia.
The cumulative duration of PPI use was statistically significant but opposite of the expected outcome. The dementia group had a lower median lifetime duration of PPI use compared with that of the nondementia group. It is difficult to determine the reason for this outcome, but it seems that for this study population, a longer duration of PPI use was not associated with an increased risk of dementia.
Finally, the exploratory endpoint analyzed vitamin B12 levels, since it has been shown that PPI use can lead to vitamin B12 deficiency and that B12 deficiency can lead to dementia.6-8 This study found that the dementia group had significantly higher vitamin B12 levels than the nondementia group. These data suggest that PPI use may not be associated with vitamin B12 deficiency. However, it is important to note that this study was unable to collect data on the use of vitamin B12 supplementation due to the unreliability of over-the-counter (OTC) and non-VA medication use records. Therefore, it is possible that the PPI group had higher rates of B12 deficiency but were effectively treated with B12 supplementation. More research is needed to determine the exact relationship between PPI use, vitamin B12 deficiency, and dementia risk.
Strengths/Limitations
Strengths of this study that support its findings include the large population size. Additionally, the use of the VA EHR allowed for a complete drug dispensing history to be collected, which improves reliability of the data.
This study also had some limitations. First, the causal relationship of PPI use and dementia cannot be proven using a retrospective cohort design. This study’s design can show association, but it cannot prove causation. Also, due to the retrospective design, exposure to PPI use could not be randomized; thus, correlation between PPI use and dementia may be explained by confounding variables that are not captured within this study. This is especially true since the baseline characteristics were not equally distributed between the 2 groups. In fact, the PPI group had higher rates of many clinical comorbidities. This imbalance may have skewed the results of the primary endpoint. Lastly, OTC PPI use and non-VA PPI prescriptions were not available. Therefore, some of the patients included in the non-PPI group may have been PPI users if they received PPIs from OTC or non-VA sources, which could skew the results.
Conclusion
This study showed a significant association between PPI use and dementia within the veteran study population. The study also showed a significant association between PPI use and dementia within the secondary endpoint of individual PPI agent. Higher cumulative dose and duration of PPI use did not seem to increase risk of dementia. Finally, PPI use was not associated with significantly low vitamin B12 levels. More studies are needed to determine causation of dementia and its risk factors.
Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Sioux Falls VA Health Care System.
Proton pump inhibitors (PPIs) have become the mainstay of therapy in the treatment of acid-related disorders since their introduction in 1989. Due to their high potency, excellent tolerability, and generic availability, PPIs have largely replaced histamine-2 receptor antagonists for gastric problems. Since they were first released on the market, the use of PPIs has continued to rise in both the hospital and primary care settings.1 However, this rapid growth has led to the concern of overutilization. A study conducted at the Department of Veterans Affairs (VA) Ann Arbor Health Care System found that out of 946 patients in the ambulatory care setting taking PPIs, only 35% were appropriately prescribed PPIs.2
Although the short-term adverse effects of PPI use seem minimal, chronic PPI use consequences are a growing concern. Chronic PPI use is associated with increased risks of osteoporosis, pneumonia, and Clostridium difficile infections.3 Another long-term risk that has been associated with chronic PPI use is dementia. Dementia is a cognitive syndrome that is characterized by a progressive decline beyond what is expected in normal aging in 1 or more of the cognitive domains of memory, language, orientation, learning capacity, executive function, or social cognition.4 Because it interferes with activities of daily living, dementia is a major cause of disability in the elderly and is an immense burden for caregivers. Currently, about 47 million people globally live with dementia.5 This number is projected to nearly triple by 2050 to 132 million.5 With no cure, identification of risk factors and creation of protective measures are critical in decreasing the prevalence of dementia.
Although the exact pathophysiology behind the link between PPIs and dementia is unknown, several theories exist. One such theory is that PPI-induced vitamin B12 deficiency leads to cognitive decline.6,7 Another theory suggests that PPIs can directly cause dementia by inhibiting enzymes that normally degrade β amyloid.8 This leads to increased levels of β-amyloid plaques, which is a known characteristic of dementia patients. This theory is derived from animal studies that have shown increased amyloid levels in the brains of mice given PPIs.8
Current studies are conflicting regarding the association between PPIs and dementia. Two German prospective, cohort studies found statistically significant increased risks of dementia in patients taking PPIs with hazard ratios (HR) of 1.38 (95% CI, 1.04-1.83) and 1.44 (95% CI, 1.36-1.52), respectively.9,10 A study conducted in Taiwan also found an increased risk of dementia among PPI users with a HR of 1.22 (95% CI, 1.05-1.42).11 On the contrary, other studies have failed to show an increased risk of dementia with PPI use. In fact, Goldstein and colleagues found a decreased risk of dementia in PPI users with a HR of 0.78 (95% CI, 0.76-0.93).12 This study was an observational study conducted in the US using data from the National Alzheimer’s Coordinating Center database.12 Another recent retrospective study conducted in Finland showed that PPI use was not associated with a significantly increased risk of Alzheimer disease.13
Much is unknown about the cause of dementia, and no curative treatment exists. Investigation into potential risk factors for dementia can lead to the development of preventative measures, which can lead to significant improvement in quality of life for both patients and caregivers. Current studies regarding the association between PPIs and dementia are conflicting, and to our knowledge, no study analyzing the effects of PPIs and dementia has been conducted within the veteran population specifically. The objective of the current study is to investigate the association between PPI use and dementia in the veteran population.
Methods
This study is a retrospective, cohort, single-center, chart review study conducted at the Sioux Falls Veteran Affairs Health Care System (SFVAHCS). Data were extracted from the VA electronic health record (EHR) from January 1, 2005 through December 31, 2015. The study included both currently living and deceased veterans who received ≥ 2 documented outpatient visits at the SFVAHCS during the study time frame. Patients also had to be aged ≥ 60 years at the start of the study period. Patients were excluded if they received only a ≤ 30-day PPI prescription. Patients with dementia related to head trauma, acute intoxication, or other known diseases were excluded.
To analyze the primary endpoint of association between PPI use and dementia, the study compared the rate of dementia in a cohort of veterans who had received an outpatient prescription for a PPI within the study time frame vs the rate of dementia in a random, equal number of veterans who had never been prescribed PPIs within the study time frame. In this study, veterans were classified as having dementia if they had a diagnosis of dementia based on ICD-9 or ICD-10 codes (Table 1), or if they had been prescribed medications used to treat dementia (donepezil, ergoloid mesylates, galantamine, memantine, and rivastigmine).
Secondary endpoints included analysis of the effects of PPI agent, PPI dose, and PPI duration on the risk of dementia. For the PPI dose analysis, cumulative doses were converted into defined daily doses (DDDs) using the World Health Organization calculation to equalize the different potencies of PPI agents (Table 2).14 In addition, the effect of PPI use on vitamin B12 levels was analyzed as an exploratory endpoint to investigate the hypothesis that PPI may be associated with vitamin B12 deficiency, which in turn may be associated with dementia.6,7
Baseline characteristics were collected to determine the variability between the treatment and control group. Data collected included age, gender, past medical history of diseases that may increase risk of dementia, and anticholinergic drug use. Anticholinergic drugs were included if they were classified as having “definite anticholinergic effects” based on the Aging Brain Care Anticholinergic Burden Scale (Appendix).15
Statistical Analysis
The primary endpoint was analyzed using a χ2 for association test. For the secondary endpoints, a χ2 for association test was used for endpoints with nominal data, and the Mood median test was used for endpoints with continuous data. The exploratory endpoint analyzing vitamin B12 levels was analyzed with the Mood median test. A P value of < .05 was defined as being statistically significant. Power analysis was not performed since all veterans who met the criteria were included in the study.
Results
Records of 23,656 veterans were included in the study with 11,828 veterans in both the PPI cohort and the non-PPI cohort (Table 3).
Primary Endpoint
Within the PPI group, 1,119 (9.5%) veterans had dementia compared with only 740 (6.3%) veterans in the non-PPI group. There was a statistically significant association between PPI use and dementia (P < .001). These results yielded an odds ratio of 1.55 for dementia risk in PPI users vs nonusers and a relative risk increase of 51.4% for dementia risk with PPI use compared with no PPI use.
Secondary Endpoints
Users of rabeprazole had the highest rate of dementia (12.8%), followed by lansoprazole (10.9%), omeprazole (9.7%), esomeprazole (7.7%), and pantoprazole (7.0%). The rate of dementia for non-PPI users was 6.3% (P < .001). The median cumulative doses of PPIs were not significant: 597 DDDs (95% CI, 540-630) in the dementia group vs 570 DDDs (95% CI, 540-624) in the nondementia group (P = .79). The median cumulative duration of PPI use in the dementia group was 4.6 years (95% CI, 4.25-4.92) vs 5.3 years (95% CI, 5.08-5.42) in the nondementia group (P < .001).
Exploratory Endpoint
The median B12 level in the PPI group was 521 pg/mL (95% CI, 509-533) compared with 480 pg/mL (95% CI, 465-496) in the non-PPI group (P < .001). However, both groups fell within the normal range for vitamin B12 (200-900 pg/mL).16
Discussion
The aim of this study was to determine whether an association existed between PPI use and dementia. This study showed a statistically significant association between PPI use and dementia within the veteran population. This study also showed a significant association between specific PPI agents and dementia. When analyzing the individual PPI agents, the rabeprazole group yielded the strongest relationship. However, this study was not powered to evaluate and compare risks of dementia between individual PPI agents. More data are needed to determine statistical and clinical significance of associations between individual PPI agents and risk of dementia.
The veterans with dementia had a higher median cumulative PPI dose than did the veterans without dementia; however, the results were not statistically significant. Therefore, the data cannot correlate higher doses of PPI use to increased risk of dementia.
The cumulative duration of PPI use was statistically significant but opposite of the expected outcome. The dementia group had a lower median lifetime duration of PPI use compared with that of the nondementia group. It is difficult to determine the reason for this outcome, but it seems that for this study population, a longer duration of PPI use was not associated with an increased risk of dementia.
Finally, the exploratory endpoint analyzed vitamin B12 levels, since it has been shown that PPI use can lead to vitamin B12 deficiency and that B12 deficiency can lead to dementia.6-8 This study found that the dementia group had significantly higher vitamin B12 levels than the nondementia group. These data suggest that PPI use may not be associated with vitamin B12 deficiency. However, it is important to note that this study was unable to collect data on the use of vitamin B12 supplementation due to the unreliability of over-the-counter (OTC) and non-VA medication use records. Therefore, it is possible that the PPI group had higher rates of B12 deficiency but were effectively treated with B12 supplementation. More research is needed to determine the exact relationship between PPI use, vitamin B12 deficiency, and dementia risk.
Strengths/Limitations
Strengths of this study that support its findings include the large population size. Additionally, the use of the VA EHR allowed for a complete drug dispensing history to be collected, which improves reliability of the data.
This study also had some limitations. First, the causal relationship of PPI use and dementia cannot be proven using a retrospective cohort design. This study’s design can show association, but it cannot prove causation. Also, due to the retrospective design, exposure to PPI use could not be randomized; thus, correlation between PPI use and dementia may be explained by confounding variables that are not captured within this study. This is especially true since the baseline characteristics were not equally distributed between the 2 groups. In fact, the PPI group had higher rates of many clinical comorbidities. This imbalance may have skewed the results of the primary endpoint. Lastly, OTC PPI use and non-VA PPI prescriptions were not available. Therefore, some of the patients included in the non-PPI group may have been PPI users if they received PPIs from OTC or non-VA sources, which could skew the results.
Conclusion
This study showed a significant association between PPI use and dementia within the veteran study population. The study also showed a significant association between PPI use and dementia within the secondary endpoint of individual PPI agent. Higher cumulative dose and duration of PPI use did not seem to increase risk of dementia. Finally, PPI use was not associated with significantly low vitamin B12 levels. More studies are needed to determine causation of dementia and its risk factors.
Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Sioux Falls VA Health Care System.
1. Savarino V, Dulbecco P, de Bortoli N, Ottonello A, Savarino E. The appropriate use of proton pump inhibitors (PPIs): need for a reappraisal. Eur J Intern Med. 2017;37:19-24.
2. Heidelbaugh J, Goldberg K, Inadomi J. Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting. Am J Manag Care. 2010;16(9):e228-e234.
3. Heidelbaugh JJ, Kim AH, Chang R. Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5(4):219-232.
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, (DSM-5). American Psychiatric Association: Washington, DC; 2013.
5. World Health Organization. Dementia. http://www.who.int/mediacentre/factsheets/fs362/en/. Published December 12, 2017. Accessed March 10, 2019.
6. Vogiatzoglou A, Smith AD, Nurk E, et al. Cognitive function in an elderly population: interaction between vitamin B12 status, depression, and apolipoprotein E ε4: the Hordaland Homocysteine Study. Psychosom Med. 2013;75(1):20-29.
7. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442.
8. Badiola N, Alcalde V, Pujol A, et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013;8(3):e58837.
9. Haenisch B, von Holt K, Wiese B, et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci. 2015;265(5):419-428.
10. Gomm W, von Holt K, Thomé F, et al. Association between proton pump inhibitors with risk of dementia. A pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410-416.
11. Tai SY, Chien CY, Wu DC, et al. Risk of dementia from proton pump inhibitor use in Asian population: a nationwide cohort study in Taiwan. PLoS One. 2017;12(2):e0171006.
12. Goldstein FC, Steenland K, Zhao L, Wharton W, Levey AI, Hajjar I. Proton pump inhibitors and risk of mild cognitive impairment and dementia. J Am Geriatr Soc. 2017;65(9):1969-1674.
13. Taipale H, Tolppanen AM, Tiihonen M. Tanskanen A, Tiihonen J, Hartikainen S. No association between proton pump inhibitor use and risk of Alzheimer’s disease. Am J Gastroenterol. 2017;112(12):1801-1808.
14. World Health Organization Collaborating Centre for Drug Statistics Methodology. Definition and general considerations. https://www.whocc.no/ddd/definition_and_general_considera/. Updated February 7, 2018. Accessed March 13, 2019.
15. Indiana University Center for Aging Research, Aging Brain Program. Anticholinergic cognitive burden scale. http://www.idhca.org/wp-content/uploads/2018/02/DESAI_ACB_scale_-_Legal_size_paper.pdf. Updated 2012. Accessed March 10, 2019.
16. US National Library of Medicine, MedlinePlus. Vitamin B12 level. https://medlineplus.gov/ency/article/003705.htm. Updated March 7, 2019. Accessed March 13, 2019.
1. Savarino V, Dulbecco P, de Bortoli N, Ottonello A, Savarino E. The appropriate use of proton pump inhibitors (PPIs): need for a reappraisal. Eur J Intern Med. 2017;37:19-24.
2. Heidelbaugh J, Goldberg K, Inadomi J. Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting. Am J Manag Care. 2010;16(9):e228-e234.
3. Heidelbaugh JJ, Kim AH, Chang R. Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5(4):219-232.
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, (DSM-5). American Psychiatric Association: Washington, DC; 2013.
5. World Health Organization. Dementia. http://www.who.int/mediacentre/factsheets/fs362/en/. Published December 12, 2017. Accessed March 10, 2019.
6. Vogiatzoglou A, Smith AD, Nurk E, et al. Cognitive function in an elderly population: interaction between vitamin B12 status, depression, and apolipoprotein E ε4: the Hordaland Homocysteine Study. Psychosom Med. 2013;75(1):20-29.
7. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442.
8. Badiola N, Alcalde V, Pujol A, et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013;8(3):e58837.
9. Haenisch B, von Holt K, Wiese B, et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci. 2015;265(5):419-428.
10. Gomm W, von Holt K, Thomé F, et al. Association between proton pump inhibitors with risk of dementia. A pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410-416.
11. Tai SY, Chien CY, Wu DC, et al. Risk of dementia from proton pump inhibitor use in Asian population: a nationwide cohort study in Taiwan. PLoS One. 2017;12(2):e0171006.
12. Goldstein FC, Steenland K, Zhao L, Wharton W, Levey AI, Hajjar I. Proton pump inhibitors and risk of mild cognitive impairment and dementia. J Am Geriatr Soc. 2017;65(9):1969-1674.
13. Taipale H, Tolppanen AM, Tiihonen M. Tanskanen A, Tiihonen J, Hartikainen S. No association between proton pump inhibitor use and risk of Alzheimer’s disease. Am J Gastroenterol. 2017;112(12):1801-1808.
14. World Health Organization Collaborating Centre for Drug Statistics Methodology. Definition and general considerations. https://www.whocc.no/ddd/definition_and_general_considera/. Updated February 7, 2018. Accessed March 13, 2019.
15. Indiana University Center for Aging Research, Aging Brain Program. Anticholinergic cognitive burden scale. http://www.idhca.org/wp-content/uploads/2018/02/DESAI_ACB_scale_-_Legal_size_paper.pdf. Updated 2012. Accessed March 10, 2019.
16. US National Library of Medicine, MedlinePlus. Vitamin B12 level. https://medlineplus.gov/ency/article/003705.htm. Updated March 7, 2019. Accessed March 13, 2019.