natgillin/translations-raw huggingface dataset:
Der var også en lille stigning i faste- blodglucose og i total kolesterol hos de duloxetin- behandlede patienter i modsætning til gruppen, der modtog standard - behandling.
30 duloxetine-treated patients while those laboratory tests showed a slight decrease in the routine care group.
29 Duloxetin er en kombineret serotonin - (5- HT) og noradrenalin (NA) - genoptagelseshæmmer.
Duloxetine is a combined serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor.
I dyreforsøg fører forhøjet niveau af 5- HT og NA i den sakrale ende af rygsøjlen til øget urethral tonus via en forstærket nervus pudendus- stimulering af urinrørets tværstribede lukkemuskel kun i opbevaringsfasen af vandladningscyklussen.
In animal studies, increased levels of 5-HT and NE in the sacral spinal cord, lead to increased urethral tone via enhanced pudendal nerve stimulation to the urethral striated sphincter muscle only during the storage phase of the micturition cycle.
I alle fire forsøg havde den duloxetin- behandlede gruppe en gennemsnitlig reduktion i Incontinece Episode Frequence (IEF) på 50% eller mere sammenlignet med 33% i den placebo- behandlet gruppe.
Differences were observed
Forskellene blev observeret ved hvert besøg efter medicinering i 4 uger (duloxetin 54% og placebo 22%), 8 uger (52% og 29%) og 12 uger (52% og 29%).
31 at each visit after 4 weeks (duloxetine 54%, and placebo 22%), 8 weeks (52% and 29%), and 12 weeks (52% and 33%) of medication.
I et yderligere forsøg, som var begrænset til patienter med svær stressinkontinens, blev alle responser på duloxetin opnået inden for 2 uger.
In an additional study limited to patients with severe SUI, all responses with duloxetine were achieved within 2 weeks.
Det primære
Patients meeting diagnostic criteria for major depressive disorder were excluded from these trials.
30 endepunkt var den ugentlige middelværdi af 24- timers gennemsnitlig smerte, som blev noteret hver dag af patienterne i dagbog målt på en 11- punkts Likert skala.
The primary outcome measure was the weekly mean of 24-hour average pain, which was collected in a daily diary by patients on an 11-point Likert scale.
5. 2 Farmakokinetiske egenskaber
32 5.2 Pharmacokinetic properties
25% længere hos ældre), men omfanget af
Age: pharmacokinetic differences have been identified between younger and elderly females (≥ 65 years) (AUC increases by about 25% and half-life is about 25% longer in the elderly), although the magnitude of these changes is not sufficient to justify adjustments to the dose.
5. 3 Prækliniske sikkerhedsdata
33 5.3 Preclinical safety data
Hunrotter, som fik duloxetin før og under parring samt i den tidlige drægtighedsperiode, havde nedsat fødeindtagelse og kropsvægt, afbrydelse af brunstcyklussen, et nedsat indeks for levende fødsler og overlevelse af afkom samt forsinket vækst hos afkommet ved udsættelse for systemisk påvirkning estimeret til at være højst ved den maksimale kliniske eksponering (AUC).
Female rats receiving duloxetine before and during mating and early pregnancy had a decrease in maternal food consumption and body weight, oestrous cycle disruption, decreased live birth indices and progeny survival, and progeny growth retardation at systemic exposure levels estimated to be at the most at maximum clinical exposure (AUC).
I et embryo - toxicitetstudie foretaget på kaniner blev der observeret en højere incidens af kardiovaskulære - og knogle- deformationer, hvor hunkaninerne blev udsat for systemiske påvirkninger under den maksimale kliniske eksponering (AUC).
In an embryotoxicity study in the rabbit, a higher incidence of cardiovascular and skeletal malformations was observed at systemic exposure levels below the maximun clinical exposure (AUC).
Hypromellose Hydroxypropylmethylcelluloseacetatsuccinat
Hypromellose.
Saccharose Saccharosekugler Talcum Titandioxid (E171) Triethylcitrat.
Hydroxypropyl methylcellulose acetate succinate Sucrose Sugar spheres Talc Titanium dioxide (E171) Triethyl citrate.
Gelatine, natriumlaurilsulfat, titandioxid (E171), indigotin (E132), og Edible black ink.
Gelatin Sodium Lauryl Sulfate Titanium Dioxide (E171) Indigo Carmine (E132) Edible Black Ink.
32 Edible black ink:
Edible Ink:
Syntetisk sort jernoxid (E172), propylenglycol og Shellac
Black Iron Oxide-Synthetic (E172) Propylene glycol Shellac
6. 5 Emballagetype og pakningsstørrelser
34 6.5 Nature and contents of container
Pakninger med 28 og 56 kapsler.
Packs of 28 and 56 capsules.
Hjælpestoffer:
Excipients: sucrose 8.6 mg.
Mat hvid kapselbund med påskriften "30 mg" og mat blå kapseltop med påskriften "9543".
Opaque white body, imprinted with ‘ 30 mg’ and an opaque blue cap, imprinted with ‘ 9543’.
Voksne Startdosering samt den anbefalede vedligeholdelsesdosering er 60 mg daglig uden hensyntagen til måltider.
Adults The starting and recommended maintenance dose is 60 mg daily with or without food.
5. 2).
However, caution should be exercised when treating the elderly (see section 5.2).
4. 4).
Children and adolescents There is no experience in children (see section 4.4).
4. 3 og 5. 2).
Hepatic impairment ARICLAIM should not be used in patients with liver disease resulting in hepatic impairment (see sections 4.3 and 5.2).
Dosisjustering er ikke nødvendig til patienter med let eller moderat nedsat nyrefunktion (kreatinin - clearance 30- 80 ml/ min).
Renal insufficiency No dosage adjustment is necessary for patients with mild or moderate renal dysfunction (creatinine clearance 30 to 80 ml/ min).
4. 3).
ARICLAIM should not be used in patients with severe renal impairment (creatinine clearance < 30 ml/ min; see section 4.3)..
Pludselig afbrydelse af behandlingen bør undgås.
36 Discontinuation of treatment Abrupt discontinuation should be avoided.
Ved forekomst af utålelige symptomer efter en nedsættelse af dosis eller ved seponering kan det overvejes at vende tilbage til den tidligere ordinerede dosis.
When stopping treatment with ARICLAIM the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions (see sections 4.4 and 4.8). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered.
ARICLAIM må ikke anvendes sammen med ikke- selektive, irreversible monoaminooxidase- hæmmere
Concomitant use of ARICLAIM with nonselective, irreversible Monoamine Oxidase Inhibitors (MAOIs) is contraindicated (see section 4.5).
4. 5).
ARICLAIM should not be used in combination with fluvoxamine, ciprofloxacin or enoxacine (i. e. potent CYP1A2 inhibitors) since the combination results in elevated plasma concentrations of duloxetine (see section 4.5).
Mani og krampeanfald ARICLAIM skal anvendes med forsigtighed til patienter med en anamnese med mani eller en diagnose med bipolar forstyrrelse og/ eller krampeanfald.
Mania and seizures ARICLAIM should be used with caution in patients with a history of mania or a diagnosis of bipolar disorder, and/ or seizures.
Mydriasis Der er rapporteret om tilfælde af mydriasis i forbindelse med duloxetin, og der skal derfor udvises forsigtighed ved udskrivning af ARICLAIM til patienter med forhøjet intraokulært tryk eller til patienter med risiko for akut snævervinklet glaukom.
Mydriasis Mydriasis has been reported in association with duloxetine, therefore, caution should be used when prescribing ARICLAIM to patients with increased intraocular pressure, or those at risk of acute narrow-angle glaucoma.
4. 3.
For patients with severe renal impairment, see section 4.3. ee section 4.2 for information on patients with mild or moderate renal dysfunction.
4. 2.
Use with antidepressants
35 Samtidig brug af antidepressiva Der bør udvises forsigtighed ved samtidig brug af ARICLAIM og antidepressiva.
37 Caution should be exercised when using ARICLAIM in combination with antidepressants.
Specielt anbefales det ikke at kombinere med selektive reversible MAO- hæmmere.
In particular the combination with selective reversible MAOIs is not recommended.
Perikum Uønskede virkninger kan forekomme hyppigere ved samtidig brug af ARICLAIM og naturlægemidler samt kosttilskud indeholdende perikum (hypericum perforatum).
St John’ s wort Undesirable effects may be more common during concomitant use of ARICLAIM and herbal preparations containing St John’ s wort (Hypericum perforatum).
Depression, selvmordsforestillinger og - adfærd Selvom ARICLAIM ikke er indiceret til behandling af depression, findes det aktive stof (duloxetin) også som et antidepressivt lægemiddel.
Depression, suicidal ideation and behaviour Although ARICLAIM is not indicated for the treatment of depression, its active ingredient (duloxetine) also exists as an antidepressant medication.
Depression er forbundet med en øget risiko for selvmords - tanker, at forvolde skade på sig selv og selvmord (selvmordsrelaterede handlinger).
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events).
Det er generel klinisk erfaring med alle antidepressive behandlinger, at risikoen for selv - mord kan stige i de tidlige stadier af behandlingen.
It is general clinical experience that the risk of suicide may increase in the early stages of recovery.
En metaanalyse af placebokontrollerede kliniske forsøg af antidepressive læge - midler til behandling af psykiske lidelser, viste en lille forøget risiko for selvmordsadfærd med anti - depressiva sammenlignet med placebo hos patienter under 25 år.
A meta-analysis of placebo- controlled clinical trials of antidepressant medicinal products in psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.
4. 8).
Cases of suicidal thoughts and suicidal behaviours have been reported during duloxetine therapy or early after treatment discontinuation (see section 4.8).
Hvis patienten, under ARICLAIM- behandling, udvikler agitation eller depressive symptomer, bør en specialist konsulteres, eftersom depression er en alvorlig medicinsk tilstand.
If while on ARICLAIM therapy, the patient develops agitation or depressive symptoms, specialised medical advice should be sought, as depression is a serious medical condition.
4. 2)
If a decision to initiate antidepressant pharmacological therapy is taken, the gradual discontinuation of ARICLAIM is recommended (see section 4.2).
Der mangler data på langtidssikkerhed hos børn og unge hvad angår vækst, modning, kognitiv - og adfærdsudvikling.
In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
Det anbefales at udvise forsigtighed hos patienter i behandling med antikoagulantia og/ eller lægemidler, som påvirker trombocytfunktionen, og hos patienter med kendt blødningstendens.
Caution is advised in patients taking anticoagulants and/ or medicinal products known to affect platelet function, and in patients with known bleeding tendencies.
Hyponatriæmi Hyponatriæmi er i sjældne tilfælde, hovedsagligt hos ældre, blevet rapporteret ved indgivelse af ARICLAIM.
Hyponatremia Hyponatremia has been reported rarely, predominantly in the elderly, when administering ARICLAIM.
ARICLAIM og placebo.
In clinical trials adverse events seen on abrupt treatment discontinuation occurred in approximately 45% of patients treated with ARICLAIM and 23% of patients taking placebo.
36 Risikoen for seponeringssymptomer set for SSRI og SNRI kan afhænge af flere faktorer blandt andet behandlingsvarigheden, dosis og hvor hurtigt dosis reduceres.
The risk of withdrawal symptoms seen with SSRI’ s and SNRI’ s may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction.
De mest almindelige bivirkninger er anført under punkt 4. 8.
The most commonly 38 reported reactions are listed in section 4.8.
Duloxetin bør bruges med forsigtighed til patienter i behandling med andre læge - middelstoffer, som er forbundet med leverskade.
Duloxetine should be used with caution in patients treated with other medicinal products associated with hepatic injury.
Foruden de nedenfor nævnte interaktioner er risikoen ved brug af duloxetin i kombination med andre CNS- aktive lægemidler ikke blevet systematisk undersøgt.
CNS medicinal products: the risk of using duloxetine in combination with other CNS-active medicinal products has not been systematically evaluated, except in the cases described in this section.
Som konsekvens deraf anbefales det at udvise forsigtighed, når ARICLAIM tages sammen med andre centralt virkende lægemidler eller stoffer, herunder alkohol og sederende lægemidler (benzodiazepiner, morfinlignende præparater, antipsykotika, phenobarbital, sederende antihistaminer).
Consequently, caution is advised when ARICLAIM is taken in combination with other centrally acting medicinal products and substances including alcohol and sedative medicinal products (e. g. benzodiazepines, morphinomimetics, antipsychotics, phenobarbital, sedative antihistamines).
På grund af risikoen for serotoninsyndrom må ARICLAIM ikke anvendes sammen med ikke- selektive, irreversible monoaminooxidasehæmmere (MAO- hæmmere) eller i mindst 14 dage efter afbrudt behandling med en MAO- hæmmer.
Monoamine Oxidase Inhibitors (MAOIs): due to the risk of serotonin syndrome, ARICLAIM should not be used in combination with nonselective irreversible monoamine oxidase inhibitors (MAOIs), or within at least 14 days of discontinuing treatment with an MAOI.
Risikoen for serotoninsyndrom for selektive, reversible MAO- hæmmere som moclobemid er lavere.
For selective, reversible MAOIs, like moclobemide, the risk of serotonin syndrome is lower.
4. 4).
However, the concomitant use of ARICLAIM with selective, reversible MAOIs is not recommended (see section 4.4).
Der er i sjældne tilfælde rapporteret om serotoninsyndrom hos patienter i behandling med SSRI- præparater (f. eks. paroxetin eller fluoxetin) sammen med serotonerge lægemidler.
Serotonin syndrome: in rare cases, serotonin syndrome has been reported in patients using SSRIs (e. g. paroxetine, fluoxetine) concomitantly with serotonergic medicinal products.
Det anbefales at udvise forsigtighed, hvis ARICLAIM anvendes sammen med serotonerge antidepressiva som SSRI- præparater, tricykliske præparater (f. eks. clomipramin eller amitriptylin), perikum (hypericum perforatum), venlafaxin eller triptaner, tramadol, pethidin og tryptophan.
Caution is advisable if ARICLAIM is used concomitantly with serotonergic antidepressants like SSRIs, tricyclics like clomipramine or amitriptyline, St John’ s wort (Hypericum perforatum), venlafaxine or triptans, tramadol, pethidine and tryptophan.
37 Duloxetins virkning på andre lægemidler Lægemidler, der metaboliseres via CYP1A2:
Effect of duloxetine on other medicinal products Medicinal products metabolised by CYP1A2:
Theophyllins (et CYP1A2- substrat) farmakokinetik blev ikke påvirket signifikant ved samtidig behandling med duloxetin (60 mg to gange daglig).
The pharmacokinetics of theophylline, a CYP1A2 39 substrate, were not significantly affected by co-administration with duloxetine (60 mg twice daily).
Det anbefales at udvise forsigtighed ved administration af ARICLAIM sammen med præparater, som hovedsageligt metaboliseres via CYP2D6 (risperidon, tricycliske antidepressiva [TCA’ er] såsom nortriptylin, amitriptylin og imipramin), specielt hvis disse præparater har et snævert terapeutisk indeks (som f. eks. flecainid, propafenon og metoprolol).
Caution is advised if ARICLAIM is co-administered with medicinal products that are predominantly metabolised by CYP2D6 (risperidone, tricyclic antidepressants [TCAs] such as nortriptyline, amitriptyline, and imipramine) particularly if they have a narrow therapeutic index (such as flecainide, propafenone and metoprolol).
Samtidig administration af duloxetin med aluminium - og magnesium - holdige antacida eller med famotidin har ingen signifikant virkning på absorptionshastigheden eller absorptionsfraktionen af duloxetin efter en oral dosis på 40 mg.
Effects of other medicinal products on duloxetine Antacids and H2 antagonists: co-administration of duloxetine with aluminium- and magnesium- containing antacids or duloxetine with famotidine had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral dose.
Da CYP1A2 er involveret i metaboliseringen af duloxetin, vil samtidig behandling med duloxetin og potente CYP1A2- hæmmere sandsynligvis medføre højere koncentrationer af duloxetin.
Inhibitors of CYP 1A2: because CYP1A2 is involved in duloxetine metabolism, concomitant use of duloxetine with potent inhibitors of CYP1A2 is likely to result in higher concentrations of duloxetine.
Fluvoxamin (100 mg én gang daglig), en potent CYP1A2- hæmmer, mindskede den tilsyneladende plasma- clearance for duloxetin med omtrent 77% og øgede AUC0- t 6 gange.
Fluvoxamine (100 mg once daily), a potent inhibitor of CYP1A2, decreased the apparent plasma clearance of duloxetine by about 77% and increased AUCo-t 6-fold.
Befolkningspharmakokinetiske analyser har vist, at rygere har næsten 50% lavere plasmakoncentration af duloxetin sammenlignet med ikke- rygere.
Population pharmacokinetic analyses have shown that smokers have almost 50% lower plasma concentrations of duloxetine compared with non-smokers.
Som for andre serotonerge lægemidler kan seponeringssymptomer forekomme hos det nyfødte barn, hvis moderen har indtaget duloxetin i den sidste del af graviditeten.
As with other serotoninergic medicinal products, discontinuation symptoms may occur in the neonate after maternal duloxetine use near term.
4. 7 Virkning på evnen til at føre motorkøretøj eller betjene maskiner
40 4.7 Effects on ability to drive and use machines
38 Der er ikke foretaget undersøgelser af virkningen på evnen til at føre motorkøretøj eller betjene maskiner.
No studies on the effects on the ability to drive and use machines have been performed.
4. 9 Bivirkninger
4.8 Undesirable effects
Tabel 1 viser observerede bivirkninger fra spontane rapporter samt fra placebo- kontrollerede kliniske forsøg (omfattende en total på 5253 patienter – heraf fik 3289 patienter duloxetin og 1964 patienter fik placebo).
Table 1 gives the adverse reactions observed from spontaneous reporting and in placebo-controlled clinical trials (comprising a total of 5253 patients, 3289 on duloxetine and 1964 on placebo).
Kvalme, hovedpine, mundtørhed og søvnighed.
The most commonly observed adverse reactions in patients with diabetic neuropathic pain treated with ARICLAIM were: nausea; headache, dry mouth and somnolence.
Meget almindelig (≥1/ 10, almindelig (≥1/ 100 og < 1/ 10), ikke almindelige (≥1/ 1000 og < 1/ 100), sjælden (≥1/ 10. 000 og < 1/ 1000), meget sjælden (< 1/ 10. 000) og ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
Very common (≥ 1/ 10), common (≥ 1/ 100 and < 1/ 10), uncommon (≥ 1/ 1,000 and < 1/ 100), rare (≥ 1/ 10,000 and < 1/ 1,000), very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
Nervesystemet
Cardiac Disorders
Supra - ventrikulær arytmi, hovedsagelig atrieflimren
Supra- ventricular arrhythmia, mainly atrial fibrillation
Hovedpine (13, 8%) Somnolens (10, 7%)
Headache (13.8%) Somnolence (10.7%) Eye Disorders
Mave- tarmkanalen Kvalme (21, 7%) Mundtørhed (13, 2%) Nyrer og urinveje
Gastrointestinal Disorders Nausea (21.7%) Dry mouth (13.2%)
Besværet vandladning Tilbageholdelse af urin Dysuria Natlig vandladning Polyrui Nedsat urinmængde
Urinary Retention Urinary hesitation Dysuria Nocturia Polyuria Urine flow decreased
Udslæt Øget perspira - tion Nattesved
Rash Sweating increased Night sweats
Lysfølsomheds reaktioner Øget tendens til at få blå mærker Kontaktdermatitis Nældefeber Koldsved
Photo- sensitivity reactions Increased tendency to bruise Dermatitis contact Urticaria Cold sweat
Stevens - Johnson syndrom Angioneurotisk ødem
Stevens- Johnson Syndrome Angio-neurotic oedema
Knogler, led, muskler og bindevæv
Muscoskeletal and connective tissue disorders
Musculoskele - tale smerter Muskelstivhed Muskelspasmer
Musculo- skeletal pain Muscle tightness Muscle spasm
Muskelsitren
Muscle twitching
Det endokrine system Hypotyroidisme Metabolisme og ernæring
Endocrine disorders Hypo- thyroidism Metabolism and Nutrition Disorders
Nedsat appetit
Decreased Appetite
Infektioner og parasitære sygdomme Laryngitis Vaskulære sygdomme
Infections and infestations Laryngitis Vascular Disorders
Brystsmerter
Immune system disorders Hepato-biliary disorders
Anafylaktisk reaktion
Hepatitis3 Elevated liver enzymes (ALT, AST, alkaline phosphatase)
Hepatitis3 Forhøjede lever - enzymer (ALAT, ASAT, alkalisk fosfatase) Akut leverskade
Hepatic failure Jaundice
Der er også rapporteret tilfælde af tinnitus efter behandlingsophør 2 Sager med orthostatisk hypotension og synkope er blevet rapporteret - særligt i behandlingsopstarten 3 Se pkt 4. 4.
Cases of tinnitus have also been reported after treatment discontinuation.
5 Sager med aggression og angst er blevet rapporteret, især tidligt i behandlingen eller efter behandlingsophør.
3 See section 4.4 4 Cases of suicidal ideation and suicidal behaviours have been reported during duloxetine therapy or early after treatment discontinuation (see section 4.4) 5 Cases of aggression and anger have been reported particularly early in treatment of after treatment discontinuation.
De mest almindelige bivirkninger er svimmelhed, sensoriske forstyrrelser (inklusive paraesthesi), søvnforstyrrelser (inklusive søvnløshed og intense drømme), opstemthed eller angst, kvalme og/ eller opkastning, rysten, hovedpine, irritabilitet, diaré, hyperhidrosis og vertigo.
43 Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/ or vomiting, tremor, headache, irritability, diarrhoea, hyperhydrosis and vertigo are the most commonly reported reactions.
Det anbefales derfor at
Generally, for SSRIs and SNRIs, these events are mild to moderate and self-limiting, however, in some patients they may be severe and/ or prolonged.
I de kliniske 12- ugers akut fase duloxetin forsøg med patienter med diabetisk neuropatisk smerte blev der observeret en lille men statistisk signifikant stigning i faste blodglucose hos duloxetin- behandlede patienter. HbA1C var stabilt hos både duloxetin- behandlede og placebo- behandlede patienter.
HbA1c was stable in both duloxetine-treated and placebo-treated patients.
Der kendes ingen antidot mod duloxetin men i tilfælde af serotoninsyndrom, kan specifik behandling (såsom for cyproheptadin og/ eller temperatur kontrol) overvejes.
No specific antidote is known for duloxetine but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/ or temperature control) may be considered.
Duloxetin er en kombineret serotonin - (5- HT) og noradrenalin (NA) - genoptagelseshæmmer.
Duloxetine is a combined serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor.
Effekten af duloxetin som en behandling af diabetiske neuropatiske smerter blev etableret i 2 randomiserede 12- ugers, dobbeltblinde, placebokontrollerede forsøg med fast dosis hos voksne (22 til 88 år), som havde haft diabetiske neuropatiske smerter i mindst 6 måneder.
44 The efficacy of duloxetine as a treatment for diabetic neuropathic pain was established in 2 randomised, 12-week, double-blind, placebo-controlled, fixed dose studies in adults (22 to 88 years) having diabetic neuropathic pain for at least 6 months.
65% duloxetinbehandlede patienter mod 40% placebobehandlede.
At least 30% reported pain reduction was recorded in approximately 65% of duloxetine treated patients versus 40% for placebo.
Hos patienter, som ikke havde oplevet somnolens, blev der observeret klinisk respons hos 47% af de duloxetinbehandlede patienter og 27% af de placebobehandlede patienter.
For patients not experiencing somnolence, clinical response was observed in 47% of patients receiving duloxetine and 27% patients on placebo.
Den absolutte orale biotilgængelighed for duloxetin ligger på 32- 80% (gns. på 50%).
The absolute oral bioavailability of duloxetine ranged from 32% to 80% (mean of 50%).
Ca.
These changes do not have any clinical significance.