Pääteiden lyhyen aikavälin matka-aikaennusteet

320073

Demokratia ja ihmisoikeudet: Tavoitteet ja sisällöt opettajankoulutuksessa

Opetus- ja kulttuuriministeriö antoi 26.9.2013 selvityshenkilöille toimeksiannon selvittää demokratiaan ja ihmisoikeuksiin liittyvien tavoitteiden toteutumista ja sisältöjen käsittelyä yliopistojen ja ammatillisten opettajakorkeakoulujen opettajankoulutuksessa. Selvitystyön tavoitteena oli 1) laatia tilannekatsaus demokratian ja ihmisoikeuksien sisältöjen käsittelystä opettajankoulutuksessa ja koulutukseen kuuluvassa harjoittelussa, 2) arvioida, millaiset valmiudet tulevat opettajat saavat opettajankoulutuksessa demokratian ja ihmisoikeuksien keskeisten kysymysten käsittelyyn ja 3) tuottaa suosituksia demokratia- ja ihmisoikeuskysymyksien opetuksen ja opintojen kehittämiseksi opettajankoulutuksessa ja siihen kuuluvassa harjoittelussa. Selvitystyössä on hyödynnetty tausta-aineistona politiikkalinjauksia, viranomaisasiakirjoja sekä aiempia aiheeseen liittyviä selvityksiä ja tutkimuksia. Selvitystyön keskeistä aineistoa ovat opettajankoulutusten opetussuunnitelmat, kuulemistilaisuuksissa ja haastatteluissa kerätyt tiedot sekä kirjalliset lausunnot. Haastatteluihin osallistui yhteensä 105 yliopistollisten opettajankoulutuslaitosten tai yksiköiden, harjoittelukoulujen ja opiskelijoiden edustajaa, 44 ammatillisten opettajankoulutuslaitosten opettajaa ja opiskelijaa sekä neljä ammattikorkeakoulujen sosiaalialan varhaiskasvatuksen opettajaa. Selvitystyön käynnistävään esiseminaariin osallistui 24 henkilöä. Kirjallinen lausunto saatiin 23 sidosryhmältä (kansalaisjärjestöt, eri ministeriöt, opiskelijajärjestöt, OAJ) sekä 12 opettajankoulutukseen osallistuvalta yliopistolliselta ainelaitokselta tai taidealan yliopistolta. Opettajankoulutuksen eri osapuolten kuulemisten sekä opetussuunnitelmien tarkastelun perusteella on ilmeistä, että kaikissa yksiköissä pidetään demokratiaa ja ihmisoikeuksia koulutuksen keskeisinä arvolähtökohtina. Ne liittyvät myös toimintakulttuuriin. Demokratiaa ja ihmisoikeuksia suoranaisesti käsitteleviä opintojaksoja sisältyy eri koulutuksiin hyvin vähän. Useimmissa yksiköissä nämä teemat tulevat kuitenkin esille monissa eri yhteyksissä, esimerkiksi kasvatustieteen filosofis-yhteiskunnallisilla jaksoilla, monikulttuurisuusopinnoissa ja eräisiin oppiaineisiin liittyvillä ainedidaktisilla jaksoilla. Eri yksiköiden profiileissa on eroja, ja mikäli yksikössä tehdään demokratia- ja ihmisoikeuskysymyksiin liittyvää tutkimusta, se myös tukee tämän ainepiirin käsittelyä koulutuksessa. Toimintakulttuuria on pyritty kehittämään osallistavaan suuntaan. Opiskelijoilla on mahdollisuus osallistumiseen virallisesti ja edustuksellisesti, minkä lisäksi kaikissa yksiköissä on erilaisia epävirallisia osallistamisen muotoja. Harjoittelukouluissa esiintyy monia käytänteitä, jotka tukevat oppilaiden osallisuutta ja joihin myös opettajaopiskelijoita pyritään perehdyttämään. Yliopistot ja ammatilliset opettajankoulutuslaitokset kehittävät opetussuunnitelmiaan autonomisesti. Erityisesti ihmisoikeustoimijat näkivät tämän vaikeuttavan ihmisoikeuskysymysten tuomista näkyväksi osaksi opettajankoulutusta. Selvityshenkilöt esittävät useita suosituksia, jotka koskevat opettajankoulutuksen ja siihen liittyvän harjoittelun sekä opettajankoulutusyksiköiden toimintakulttuurin kehittämistä. Ihmisoikeuskysymykset, demokratia ja osallistaminen on syytä tuoda nykyistä näkyvämmäksi ja laajemmaksi osaksi koulutusta. Opettajaopiskelijoiden on saatava paitsi tietoja, myös käytännön valmiuksia ja kokemuksia, jotka mahdollistavat ihmisoikeuksia ja osallisuutta kunnioittavan toiminnan opetustyössä. Tämä edellyttää opettajankouluttajien ammatillisen kehittymisen tukemista sekä verkostoitumista ja yhteistyötä. Yhteistyöllä tarkoitamme paitsi eri koulutusyksiköiden välistä, myös koulutusyksiköiden ja kansalaisjärjestöjen välistä yhteistyötä. Erityisen tärkeää on resurssien suuntaaminen demokratia- ja ihmisoikeuskasvatuksen tutkimukseen

Demokratia- ja ihmisoikeuskasvatus Suomessa : Tilannekuva ja suositukset 2023

Tässä raportissa on selvitetty demokratia- ja ihmisoikeuskasvatukselle asetettujen tavoitteiden toteutumista. Kyseiset tavoitteet sisältävät tiedollisia, taidollisia ja asenteellisia elementtejä sekä toiminnan prosessien mahdollistumista ja toteutumista. Tietoa kerättiin laadullisin ja vuorovaikutuksellisin menetelmin, myös lapsilta, oppilailta ja opiskelijoilta. Näkökulmina raportissa ovat demokratia- ja ihmisoikeuskasvatuksen yhdenvertainen toteutuminen, yhdenvertaisuuden edistäminen sekä lasten ja nuorten osallistumisoikeuden toteutuminen. Selvityksen perusteella annetaan seuraavat suositukset demokratia- ja ihmisoikeuskasvatuksen kansalliseksi kehittämiseksi: 1: Kannustetaan korkeakouluja ottamaan demokratia- ja ihmisoikeuskasvatussisältöjä osaksi pakollisia opintoja opettajankoulutuksessa. 2: Määritellään demokratia- ja ihmisoikeuskasvatukselle kansallisen tason suuntaviivat -ohjelma tavoitetiloineen ja resursoidaan kyseisen ohjelman toteuttamista varten kansallisen, alueellisen ja paikallisen tason kattava koordinointirakenne. 3: Huomioidaan lapset, oppilaat ja opiskelijat subjekteina demokratia- ja ihmisoikeustilanteen ja -kasvatuksen arvioinnissa ja niihin liittyvien kehittämistoimien toteuttamisessa.Tämä julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa. (tietokayttoon.fi) Julkaisun sisällöstä vastaavat tiedon tuottajat, eikä tekstisisältö välttämättä edusta valtioneuvoston näkemystä

Cognitive and Neuropsychiatric Symptom Differences in Early Stages of Alzheimer's Disease: Kuopio ALSOVA Study

Background/Aim: Alzheimer’s disease (AD) causes impairment in memory and other cognitive functions as well as neuropsychiatric symptoms and limitations in the activities of daily living (ADL). The aim of this study was to examine whether demographic variables, dementia severity, ADL and neuropsychiatric symptoms are associated with cognition in very mild or mild AD. Methods: We analyzed the baseline data of 236 patients with very mild or mild AD participating in a prospective AD follow-up study (ALSOVA). The Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery total score was used in the evaluation of the global cognitive performance. Results: Cognition was associated with dementia severity and ADL but not with neuropsychiatric symptoms. ADL functions were associated with both cognitive performance and neuropsychiatric symptoms. Conclusion: Even patients with very mild or mild AD may exhibit neuropsychiatric symptoms not related to cognitive impairment. The results of this study emphasize the importance of taking a multidimensional approach to the diagnostic and prognostic evaluation of AD patients already in the early stages of the disease

Effect of strain, wood substrate and cold treatment on the yield and β-glucan content of Ganoderma lucidum fruiting bodies

Wood residues from forestry industries can be potential raw materials for specialty and edible mushroom production. The aim of this study was to evaluate the suitability of wood residues for the cultivation of Ganoderma lucidum originating from boreal forests. The substrates tested included sawdust and wood chips of Betula spp., Populus tremula, Picea abies, Pinus sylvestris and Larix sp. The suitability of the substrates and the ability of the strains to develop fruiting bodies and produce β-glucan were evaluated. Fruiting body formation was supported by applying two different cold shock treatments to substrate bags. The highest yields were observed with MUS192 strain and Betula spp. and P. tremula wood-based substrates. β-Glucan content in the fruiting bodies was highest with the MUS75 and P. tremula wood-based substrate. Based on these findings, the combination of P. tremula wood residues and the MUS192 strain is proposed to enhance the yieldand β-glucan content of the fruiting bodies. A cold treatment of 5 °C is suggested to induce primordia formation and to increase fruiting probability. This is the first time that strains of G. lucidum originating from boreal forests have been compared and successfully cultivated simulating commercial indoor cultivation.202

Seasonal variation of CCN concentrations and aerosol activation properties in boreal forest

As a part of EUCAARI activities, the annual cycle of cloud condensation nuclei (CCN) concentrations and critical diameter for cloud droplet activation as a function of supersaturation were measured using a CCN counter and a HTDMA (hygroscopicity tandem differential mobility analyzer) at SMEAR II station, Hyytiälä, Finland. The critical diameters for CCN activation were estimated from (i) the measured CCN concentration and particle size distribution data, and (ii) the hygroscopic growth factors by applying κ-Köhler theory, in both cases assuming an internally mixed aerosol. The critical diameters derived by these two methods were in good agreement with each other. The effect of new particle formation on the diurnal variation of CCN concentration and critical diameters was studied. New particle formation was observed to increase the CCN concentrations by 70–110%, depending on the supersaturation level. The average value for the κ-parameter determined from hygroscopicity measurements was κ = 0.18 and it predicted well the CCN activation in boreal forest conditions in Hyytiälä. The derived critical diameters and κ-parameter confirm earlier findings with other methods, that aerosol particles at CCN sizes in Hyytiälä are mostly organic, but contain also more hygrosopic, probably inorganic salts like ammonium sulphate, making the particles more CCN active than pure secondary organic aerosol.Peer reviewe

Cerebrospinal fluid dynamics in idiopathic intracranial hypertension : a literature review and validation of contemporary findings

Publisher Copyright: © 2021, The Author(s).Background: Idiopathic intracranial hypertension (IIH) is a rare disease of unknown aetiology related possibly to disturbed cerebrospinal fluid (CSF) dynamics and characterised by elevated intracranial pressure (ICP) causing optic nerve atrophy if not timely treated. We studied CSF dynamics of the IIH patients based on the available literature and our well-defined cohort. Method: A literature review was performed from PubMed between 1980 and 2020 in compliance with the PRISMA guideline. Our study includes 59 patients with clinical, demographical, neuro-ophthalmological, radiological, outcome data, and lumbar CSF pressure measurements for suspicion of IIH; 39 patients had verified IIH while 20 patients did not according to Friedman’s criteria, hence referred to as symptomatic controls. Results: The literature review yielded 19 suitable studies; 452 IIH patients and 264 controls had undergone intraventricular or lumbar CSF pressure measurements. In our study, the mean CSF pressure, pulse amplitudes, power of respiratory waves (RESP), and the pressure constant (P0) were higher in IIH than symptomatic controls (p < 0.01). The mean CSF pressure was higher in IIH patients with psychiatric comorbidity than without (p < 0.05). In IIH patients without acetazolamide treatment, the RAP index and power of slow waves were also higher (p < 0.05). IIH patients with excess CSF around the optic nerves had lower relative pulse pressure coefficient (RPPC) and RESP than those without (p < 0.05). Conclusions: Our literature review revealed increased CSF pressure, resistance to CSF outflow and sagittal sinus pressure (SSP) as key findings in IIH. Our study confirmed significantly higher lumbar CSF pressure and increased CSF pressure waves and RAP index in IIH when excluding patients with acetazolamide treatment. In overall, the findings reflect decreased craniospinal compliance and potentially depleted cerebral autoregulation resulting from the increased CSF pressure in IIH. The increased slow waves in patients without acetazolamide may indicate issues in autoregulation, while increased P0 could reflect the increased SSP.Peer reviewe

Dyslipidemiat : KÄYPÄ HOITO -SUOSITUS (Päivitystiivistelmä)

Käypä hoito -suositus. Päivitystiivistelm

Ambulatory Monitoring Uncorrected for Placebo Overestimates Long-term Antihypertensive Action

Abstract &apos;This study compares blood pressure (BP) changes during active antihypertensive treatment and placebo as assessed by conventional and anlbulatory BP measurement. Older patients (260 years, n=337) with isolated systolic hypertension by conventional sphygrnomanometry at the clinic were rando~nized to placebo or active treatment consisting of nitrendipine (10 to 40 mgid), with the possil~le addition oF enalapril (5 10 20 mgid) ;~nd/or hydrochlorothiazide (12.5 Lo 25 mg/d). At baseline, clinic systolic/diastolic BP averaged 175186 mm Hg and 24-hour and daytimc ;~mbulatory BPs averaged 148180 and 154185 mm Hg, respectively. After 13 months (median) of active treatment, clinic BP had dropped by 22.717.0 mm Hg and 24-hour and daytime BPs by 10.514.5 and 9.714.3 mm Hg, respectively (P&lt;.001 for all). However, clinic (9.811.6 mm Hg), 24-hour (2.11 1.1 nini Hg), and daytime (2.911.0 mm Hg) BPs decreased also during placebo (P&lt;.05, except for daytime diastolic BP); these decreases represented 43%/23%, 20%/24%, and 30%/23% of the corresponding BP fall during active treatment. After subtraction of placebo effects, the net BP reductions during active treatment averaged only 12. 915.4, 8.313.4, and 6.813.2 mm Hg for clinic, 24-hour, and daytime BPs, respectively. The effect of active treatment was also subject to diurnal variation (R.05). Changes during placebo in hourly systolic and diastolic BP means amounled to (median) 21% (range, -1% to 42%) and 25% (-3% to 72%), respectively, of the corresponding changes during active treatment. In conclusion, expressed in millimeters of mercury, the effect of antihypertensive treatment on BP is larger with conventional than with ambulatory measurement. Regardless of whether BP is measured by conventional sphygmomanometry or ambulatory monitoring, a substantial proportion of the long-tern~ BP changes observed during active treatrnent may be attributed to placebo effects. Thus, ambulatory monitoring uncorrected for placebo or control observations, like conventional sphygmomanometry, overestimates BP responses in clinical trials of long duration. (Hypertension. lYY6;27[part 1]:414-420.) Key IYords blood pressure monitoring, ambulatory antihypertensive therapy clinical trials blood pressure monitoring placebo T he SYST-EUR Trial is a double-blind, placebocontrolled outcome trial in older patients with isolated systolic hypertension that the European Working Party on High Blood Pressure in the Elderly is currently conducting in Western and Eastern Europe and in 1srael.l Presently, the 3000 patients originally planned lor have been randomized. In accordance with current clinical practice,2 only conventional sphygmomanometric BP readings by an auscultating observer determine a patient&apos;s eligibility for randomization and guide the stepwise adjustments of treatment during the double-blind phase of the trial. &apos; In addition to conventional sphygmomanometry, arnbulatory BP monitoring is increasingly used in clinical trials to evaluate the magnitude and duration of the BP-lowering action of antihypertensive agents. SYST-EUR centers can opt to monitor their patients in an attempt to evaluate whether the ambulatory BP, over ancl above the clinic BP, is helplul in predicting cardiovascular events.&apos; This article builds on the data collected so Tar in the SYST-EUR Trial1 and contrasts the effects Received August 25, 1995; first decision September 18, 1995; revision accepted October 31, 1995. Correspondence to Jan A. Staessen, MD, PhD, Klinisch Labo-~;ltol.iuni Ilypertensie, Inwendige Geneeskunde-Cardiologie, U Z Gaslhuisberg, Herestraat 49, Belgiu~n. 0 L996 American Heart Association, Inc. of antihypertensive treatment and placebo as assessed by conventional sphygmomanometry and ambulatory monitoring. 11 extends the findings o l a previous article that was limited to the placebo arm of the triaL4 Methods Study Design &apos;The protocol of the SYST-EUR Trial has been published elsewhere.&apos; It was approved by the Ethics Committee of the Faculty of Medicine at the University of Leuven as well as by the institutional review committees of all participating centers. Patients were eligible (I) if they were at least 60 years old; (2) if, on a placebo during the run-in phase, their sitting SBP ranged from 160 to 219 mm Hg with a DBP below 95 mm Hg; (3) if their standing SBP was 140 mm Hg or higher; and (4) if, after having been informed, they voluntarily consented to be enrolled. The BP criteria for entry rested on the averages of six silting and six standing readings, ie, two in each position at three baseline visits I month apart. Eligil~le patients were stratifed by sex and the presence versus absence of cardiovascular complications and were randomized to double-blind treatment with active medication or placebo. Aclive treatment consisted of nitrendipine BP and Other Measurements SYST-EUR centers opting to take part in ambulatory rnonitoring were asked to perform recordings at baseline, at 6 and 12 months, and annually thereafter? Validated5.Wonitors were programmed to obtain measurements at intervals not greater than 30 minutes. The conventional BP corresponding to each ambulatory recording was the average of the two readings with patients in the sitting position obtained at the nearest clinic visit. The patients were interviewed at baseline and follow-up concerliing their smoking habits, habitual alcohol intake, and activities of daily l i~i n g .~,~ In addition, the serum activity of yglulanlyllranspeptidase was determined as an index of alcohol intake.&quot; Analysis of the Diurnal BP Profile If the ambulatory recordings were longer than 24 hours, only the first 24 hours was used for analysis. Recordiligs were excluded whenever the available readings constituted less than 80% of those program~netl or covered less than 22 consecutive hours. I&apos;he editing criterial&quot;.ll considered for tlelelion of readings from the recordings were (1) SBP&lt;DBP, (2) SBP &gt;240 or &lt;40 mm Hg, (3) DBP &gt;I40 or &lt;40 mm Hg, (4) pulse rate &gt;l50 or &lt;40 beats per minute, and (5) pulse pressure &lt;10% of SBP. The 24-hour, daytime, and nighltime pressures and hourly BP means were weighted for the time between consecutive readings. l 2 Daytime was from I0 AM to 8 PM and nighttime from mitlnight to 6 AM. These dcfnitions of daytime ancl nighttime have been used in previous s t~d i e s~~&apos;~~~ and exclude the transition periods in the morning and evening during which BP changes rapidly. The awake and sleeping periods were determined from diary cards kept by the patients on recording days.7 Statistical Analysis Database management and statistical analyses were performed with the SAS software (SAS Institute Inc). Statistical methods included Student&apos;s t test and linear regression analysis. Diurnal BP profiles, drawn from hourly BP means, were contrasted by repeated measures ANOVA,I4 considering as main effects treatment allocation (active versus placebo) and time of day. For establishment of whether the antihypertensive action was steady over 24 hours, the model also tested for a treatment-time interaction. The net treatment effect, sometimes referred to as the double delta of BP,&quot; was calculated by subtracting the mean change from baseline during placebo from the corresponding change during active treatment. The 95% confidence limits about the net treatment effect showed the times during the day when the BP reduction was significant. The reproducibility of duplicate measurements was studied by the Bland and Altman technique.lh For co~nparison of the reproducibility of various BP measurements, the repeatability coefficients were expressed as a percentage of nearly maximal variation, ie. the interval encompassing four times the S D of the averaged tluplicate measurements. Results Data Available for Analysis On May 15, 1995, 407 patients had their ambulatory BP recorded during the run-in phase of the trial and at least once after randomization. In 174 of these patients, duplicate recordings had been obtained at baseline. After patients with incomplete recordings were excluded, these numbers were 337 and 118, respectively. The 792 ambulatory recordings included in the present analysis comprised a total of 51 960 single BP readings, of which only 1.5% complied with at least one of the criteria considered for editing. In 501 recordings (63%), no single reading met the editing criteria. Because editing did not influence the results, only analyses based on unedited recordings are presented. Patient Characteristics at Randomization The patients allocated to placebo (n=169) and active treatment (n= 168) had the same characteristics at randomization. They comprised 142 men and 195 women. Cardiovascular complications were present in 94 patients. Of the 337 patients, 167 had been treated during the 6 months before they were considered for entry into the trial, 30 with diuretics, 19 with P-blockers, 21 with converting enzyme inhibitors, 33 with calcium entry blockers, and 64 with various other drugs or with a combination of several antihypertensive agents. Previous antihypertensive treatment was usually discontinued l month before the first run-in visit during placebo. The median time interval between the latter visit and randomization was 76 days (range, 36 to 300) in the previously treated patients and 70 days (range, 20 to 300) in the other patients. In all 337 patients, age averaged 7026 (5SD) years (range, 60 to 100). Body mass index was 26.153.3 kg/m2 in men and 26.554.0 kg/m2 in women. SBP at the clinic averaged 175k 12 mm Hg (range, 160 to 217) and DBP 8656 mm Hg (range, 49 to 94). The corresponding 24-hour pressures were 1485 16 mm Hg (range, 1 10 to 202) and 8059 lnln Hg (range, 58 to 138), respectively. Daytime versus awake and nighttime versus sleeping SBP and DBP did no1 differ Reproducibility of Clinic and Ambulatory Pressures at Baseline In 118 patients, ambulatory monitoring had been repeated during the run-in phase of the trial at a median interval of 33 days (range, 7 to 127). Reproducibility of the clinic pressure was studied by contrasting the averages of the two readings obtained with patients in the sitting position at two outpatient visits. Group means of the clinic and ambulatory pressures could be reproduced without significant changes in their values, except for the 24-hour, daytime, and awake SBP, which decreased (1-&apos;&lt;.05) by approximately 2 mm Hg, and for the awake DBP, which decreased (Pc.05) by 1 mm Hg Treatment Effects on Clinic and Ambulatory Pressures Follow-up averaged 13 months (median) (range, 4 to 30). Of the 337 paticnts, 310 remained on the lirst-line medication, ie, nitrendipine (n=151; daily dose, 27212 mg) or matching placebo (n=159). At the follow-up visit. second-and third-line medications had been started in 49 (1427 mg) and 21 (2226 mg) patients on active treatment and in 84 and 47 patients on placebo. Active treatment decreased the clinic and ambulatory SBP and DBP, but also during placebo these pressures tended to decline Over the follow-up period, no significant changes occurred in the patients&apos; body weight (mean change?SD, -0.123.4 kg), smoking habits (-0.625.3 g tobacco per day), alcohol intake (-0.625.3 gld), serum y-glutamyltranspeptidase activity ([email protected]%), and score for the activities of daily living (median change, 0; range, -5 to +I). Modifications over the follow-up period in these lifestyle measures and previous antihypertensive treatment were not correlated with the decrease in the ambulatory BP values in the placebo group. The changes in body weight constituted the only possible exception because they tended to be positively associated with the changes in the 24-hour DBP (regression coefficientkSE, 0.2920.16 mm tiglkg; P=.07) and in the daytime (0.3820.20 mm Hgl kg, P=.OS) and nighttime (0.3520.19 mm Hglkg, P=.07) DBPs. Treatment Effects on Diurnal BP Profiles At both baseline and follow-up, time of day was a significant (P&lt;.001) source of BP variation. At baseline, treatment allocation (!&apos;=.g6 for SBP, P=.39 for DBP) as well as the interaction terms between treatment and time of day were not significant (P=.75 and .40, respectively). These results confirmed that during the run-in phase, the diurnal BP profiles were superimposable in the two treatment arms of the trial At follow-up, active treatment shifted (P&lt;.001) the diurnal BP profile downward Disparity Between Clinic and Ambulatory Measurements At baseline, the correlation coefficients between the clinic and daytime measurements were .46 for SBP and .39 for DBP. The corresponding correlation coefficients at fc&gt;llow-up were .57 and .49 in the placebo group and .32 and .35 during active treatment (PC.001 for all correlations). Clinic SBP was on all occasions higher (P&lt;.001) than daytime SBP, ie, 21215 mm Hg at baseline, 14k17 mm Hg during placebo at follow-up, and 9&amp;19 mm Hg during active treatment. In contrast, the mean differences between the clinic and daytime DBPs were small, averaging l + 10 mm Hg at baseline as well as during placebo at follow-up and -2+ 11 mm Hg during active treatment. 1)iscussion After approximately 1 year, the net separation in the clinic pressure between the two treatment groups aver- Approximately one third of the patients enrolled in the SYST-EUR Trial undergo ambulatory monitoring, in addition to conventional sphygmomanometry. The net separation between the two treatment arms after a median follow-up of approximately 1 year was considerably smaller for the ambulatory than for the clinic pressures, ie, 4.912.0 mm Hg less for the 24-hour pressures and 6.112.2 mm Hg less for the daytime pressures. Thus, the differentiation in the clinic pressures between the two treatment groups was 55%/59% larger than observed for the 24-hour pressures and 90%/69% larger than for the daytime pressures. The currently prevails that ambulatory recordings more closely reflect a patient&apos;s habitual BP level than the few readings taken by an auscultating observer in the stressful hospital e n v i r~n m e n t .~~-~T h e present study therefore suggests that the true BP responses in a long-term randomized clinical trial are overestimated by conventional sphygmomanometry by as much as 50% to 90%. The latter estimate is in agreement with a large meta-analysis of prospective observational studies in the field of hypertension.24 A correction for regression dilution bias was calculated by introducing the so-called usual BP, defined as an individual&apos;s average BP over several years. According to these ~alculations,2~ a 12 mm Hg difference in the baseline pressure was rescaled into a 7.5 mm Hg contrast in the usual pressure. Thus, BP measurements at a single occasion (baseline) were felt to inflate the gradient in the usual pressure by approximately 60%. Staessen et a1 Ambulatoly BP Monitoring During Placebo 417 BP measurements by conventional sphygmomanometry have guided patient recruitment and therapy in most clinical trials in the field of hypertension, including all outcome trials.2Wespite their track record, conventional BP readings are subject to the so-called placebo effect, often attributed to a gradual weakening of the alerting reaction22,23 and to a regression-to-the-mean phenomenon.2&quot;-29 If conventional and anlbulatory measurements are repeated within the same subjects, the latter are characterized by greater reprodu~ibility,2~~ attributable to the absence-of digit preferen~e,&quot;~ ob- server bias,&quot;) and the white coat reaction22,2&apos;.31 but foremost to the greater number of readings averaged for calculation of the ambulatorv v a l~e s . 3~ This was confirmed in the present study, in which the clinic pressures dui-ing the placebo run-in period showed higher repeatahilily cc~cficicnts, signirying lowcr intrainclividual reproducibility, than the 24-hour and daytime pressures. Debate continues over whether ambulatory BP measurements decrease during placebo. The intra-arterially measured an~bulatory pressure has been demonstrated to remain at the same level when hypertensive patients were put on a placebo for 6 weeks.&quot;klong simiiar lines, in a 6-week study with a noninvasive recording technique,&apos;4 the ambulatory pressure fell only slightly during the initial recording hours, such that the average BP over 24 hours stayed unaffected. On balance, most publications currently favor the view that the ambulatory pressure is not subject to a placebo e f f e~t . &apos; &quot; &apos; &quot;~~-~~. -7 &quot; -~~ HOWever, few long-term studies on this subject have been published. A previous SYST-EUR publication4 based on 112 patients and limited to the placebo arm of the trial showed that after a median follow-up of 1 year the clinic SUP fell by 6.6 mm tIg (P&lt;.001) and the 24-hour and daytime SBPs by 2.4 (P&lt;.05) and 2.6 mm Hg (P=.06), respectively. The corresponding decreases in DBP were smaller, averaging only 1.4 (P-.06), 1.1, and 0.7 mm Hg.4 These estimates were of the same order of magnitude as in the present analysis, in which, because of the larger number of patients, the changes during placebo in the clinic and 24-hour DBPs also reached a level of statistical significance. The decline in the ambulatory BP values, amounting to approximately 2 mm Hg, may seem trivial and negligible. However, in relative terms they represented 43%1 23%, 20%/24%, and 30%/23% of the corresponding reductions in the clinic, 24-hour, and daytime SBPs/DBPs during active treatment. As far as the clinic pressure is vations, eg, during placebo, cannot be refuted and is part of the established culture among trialists. If this rule is true for the clinic pressure, then in opposition to the prevailing view in the literat~re,~3.1&quot;2&quot;-29,&quot;3-4&quot;t also needs to be applied for the ambulatory pressure, of which a substantial fraction may be explained by placebo-like effects. This reasoning not only involves the average 24-hour and daytime pressures but also the hourly BP means, which represent the treatment effects through the whole day. In the present study, the decreases in the hourly BP values during placebo constituted up to 70% of what was observed during active treatment. In the present study, the reduction in the clinic SBP during placebo may have been influenced by the 160 mm Hg threshold used to select the patients and by a subsequent regression-to-the-mean phenomenon. However, other mechanisms are also likely to have been at play because decreases during placebo were observed in the clinic DBP, which in all patients was lower than 95 mm Hg, as well as in the ambulatory measurements, which were not used to select the patients. Familiarization with the hospital environment or the procedure of ambulatory monitoring could be examples of such mechanisms. In addition, the present analysis demonstrated that changes in lifestyle were unlikely to be involved to a major extent. The clinic SBP was 21 mm Hg higher than the daytime pressure at baseline but only 14 and 9 mm Hg higher at follow-up during placebo and active treatment, respectively. These findings suggest that the white coat effect wears off as time goes by. It may also be attenuated by antihypertensive treatment, which probably dampens the BP surges caused by sympathetic arousal to the Staesserz et a1 Ambulatory BP Monitoring During Placebo 419 observer measuring the BP. Furthermore, the decreases in the ambulatory measurements during placebo and active treatlncnt were proportional to the BP level a1 baseline. T h e regression equations derived in the present studv vredicted that the 24-hour SBP would decrease , . by only 3.0 mm H g during active treatment in patients whose 24-hour SBP at entry was 135 mm Hg, ie, the 95th percentile in normotensive s~b j e c t s .~~h~s , in agreement with a previous report,47 prescribing antihypertensive medications to patients with a high clinic but low ambulatory pressure would not result in a substantial reduction of the habitual BP through the day. T h e issue of whether ambulatory measurements need to be corrected for placebo is not without importance, as it inherently touches o n the design of clinical trials in the field of hypertension. Some experts4x feel that ambulatory monitoring eliminates only observer bias and expectation4&quot; and does not remove regression-to-the-mean and patient-related factors that contribute to the placebo effect. Other researchers defend the point of view that ambulatory monitoring would make control observations during placebo s u p e r f l~o u s .~~ If this were true, trials making use of the new technique could investigate antihypertensive interventions just by comparing the B P levels before and after therapy. T h e present findings suggest that the latter approach may lead t o a n overestimation of the true antihypertensive effect and should therefore be abandoned at least in long-term trials. A correction for placebo may even be warranted in shortterm trials because the reproducibility data in this study showed that after a median interval of 1 month the average 24-hour and daytime SBPs decreased during placebo by 1.8 and 2.4 mm Hg, respectively. Thus, clinical trials relying on ambulatory monitoring should adhere t o the same design standards as those making use of conventional sphygmomanometry. Despite theselimitations, ambulatory monitoring, compared with conventional B P readings, offers the advantage of providing information o n B P control through the whole day and makes it possible t o economize o n sample size in crossover but not parallel group trials.&quot