Placebo effects in health and disease : how expectations shape treatment outcomes

The context in which a medical treatment is administrated influences treatment outcomes. As of today, the health care system has little knowledge about the non-specific components that contribute to the positive effect of a given therapy, often referred to as the placebo component, and how this may be harnessed in order to maximize treatment effects. The overreaching aim of this doctoral thesis is to investigate the impact of non-specific treatment components on clinical outcomes, in particular the role of expectations. More specifically, this thesis focuses on two clinically relevant, yet poorly investigated, topics: 1) Are placebo effects dependent on higher order cognitions? This was investigated among patients with intellectual disability (ID) and in an experimental setting in healthy individuals. 2) Are placebo effects affected by the duration of a chronic disease? In order to study this, outcomes from a randomized controlled trial (RCT) among fibromyalgia (FM) patients were analyzed. Study I investigated the influence of non-conscious expectations on placebo analgesia, using an implicit priming task called Scrambled Sentence Test (SST). Healthy participants were randomized to receive positive or neutral expectations via the SST, followed by a placebo manipulation with a sham analgesic device. Results demonstrated no effect of implicit priming on placebo analgesia, yet the study indicates that placebo analgesia is largely explained by prior experience of pain relief, and that the social interaction with a trustworthy clinician may have competed with the possible effect of implicit priming. Study II examined the relationship between placebo analgesia and the time (months, years) a person has been exposed to chronic disease, by assessing placebo responses in a pharmacological trial in patients with FM. Results revealed that FM duration was associated with baseline pain levels as well as placebo analgesia. These results point to the importance of early FM interventions, as the chance to harness endogenous pain regulation and to avoid chronification may be higher early in the disease course. Study III investigated how treatment expectations may shape outcomes in pharmacological clinical trials among patients with ID. The placebo component in ID clinical trials was examined by performing a meta-analysis comparing drug responses in open-label trials (with 100% certainty of getting the real drug) with drug responses in placebo-controlled trials (with 50% chance of getting the real drug). The results demonstrated placebo effects among patients with ID, as the effect of the real drug in open-label context was associated with better treatment outcomes than the same drug in a placebo-controlled context. Our study validates the notion that patients with ID are influenced by contextual factors in clinical trials in spite of severe cognitive deficits

Certainty of genuine treatment increases drug responses among intellectually disabled patients

Objective: To determine the placebo component of treatment responses in patients with intellectual disability (ID). Methods: A statistical meta-analysis comparing bias-corrected effect sizes (Hedges g) of drug responses in open-label vs placebo-controlled clinical trials was performed, as these trial types represent different certainty of receiving genuine treatment (100% vs 50%). Studies in fragile X, Down, Prader-Willi, and Williams syndrome published before June 2015 were considered. Results: Seventeen open-label trials (n = 261, 65% male; mean age 23.6 years; mean trial duration 38 weeks) and 22 placebo-controlled trials (n = 721, 62% male; mean age 17.1 years; mean trial duration 35 weeks) were included. The overall effect size from pre to post treatment in open-label studies was g = 0.602 (p = 0.001). The effect of trial type was statistically significant (p = 0.001), and revealed higher effect sizes in studies with 100% likelihood of getting active drug, compared to both the drug and placebo arm of placebo-controlled trials. We thus provide evidence for genuine placebo effects, not explainable by natural history or regression toward the mean, among patients with ID. Conclusions: Our data suggest that clinical trials in patients with severe cognitive deficits are influenced by the certainty of receiving genuine medication, and open-label design should thus not be used to evaluate the effect of pharmacologic treatments in ID, as the results will be biased by an enhanced placebo component

Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants

Background: The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. Objective: We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. Design: We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case–control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. Results: Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. Conclusions: Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD

Märkning av färdigförpackade kakor och choklad i Ängelholms kommun – Uppfyller butikerna livsmedelslagstiftningens krav på livsmedelssäkerhet?

In December 2014 the requirement increased on pre-packed food labelling when the regulation (EU) No 1169/2011 entered into force. Two important changes were that allergen information must be emphasised in the ingredients list and a minimum font size must be used for the obligatory information on food labels. It´s crucial that grocery stores follow the food legislation, so that consumers and especially those with allergies can do correct choices and use groceries in a safe way. Previous studies have shown insufficient labelling of pre-packed food, especially lack of Swedish labelling and emphasising allergens. The purpose of this study was to examine how the legislative requirements on pre-packed food labelling were observed in grocery stores in the municipality of Ängelholm. Field studies were carried out in 13 grocery stores where 10 pre-packed foods were examined in every store from criteria’s as: • Swedish labelling • Legibility, easily visible • Swedish ingredients list • Emphasised allergens • Best Before date • Contact information Interviews were also carried out with one store manager/shop assistant in every grocery store to form an opinion about the knowledge of the food legislation concerning pre-packed food and the routines to control the labelling of products in the stores. The purpose was also to see if there was any connection between good routines and how well the legislation was being observed in practice. The results of the study showed that nine out of 13 grocery stores didn’t follow the food information legislation. The most common incorrectness concerning the 130 examined products were; allergens not emphasized, information of the labeling was illegible, Swedish labelling missing. 11 of the 13 grocery stores included in the study declared that they had routines to control the labelling of products in the stores. In light of the above, it could be noted that the routines often were inadequate and not always used in practice.Kan allergiker lita på att chokladen är rätt märkt i butikerna i Ängelholm? För allergiker kan det bokstavligt talat vara livsavgörande att märkningen och informationen på produkter som choklad och kakor är korrekt i våra livsmedelsbutiker. Saknas tydlig information om allergener eller om informationen inte går att förstå p.g.a. att märkningen inte är på svenska kan en allergisk konsument i värsta fall drabbas av en svår allergisk reaktion (anafylaktisk chock). Denna reaktion kan vara dödlig om snabb vård och medicinering inte sätts in. Det är därför ytterst viktigt att den livsmedelslagstiftning som reglerar just märkning och information på färdigförpackade livsmedel följs ute i butikerna så att konsumenterna kan göra medvetna val och använda livsmedel på ett säkert sätt. För att kontrollera hur väl livsmedelslagstiftningen följs i livsmedelsbutiker då det gäller märkning av färdigförpackade kakor och choklad utfördes en studie i samarbete med Miljöenheten i Ängelholms kommun. Studien utfördes både genom kontroll av produkternas märkning och genom intervjuer med butiksansvariga. Resultatet av undersökningen visade att 9 av 13 kontrollerade butiker inte följde den gällande lagstiftningen. De vanligaste bristerna bland de totalt 130 kontrollerade produkterna var att allergener inte framhävs (t.e.x. i fet stil) i ingrediensförteckningen, att märkningen var svårläst och otydlig samt att svensk märkning saknades helt. Det är ett nedslående resultat att så många som 1/3 av produkterna hade brister i märkningen. Detta visar på att butikernas rutiner för att kontrollera märkningen är otillräcklig och kanske inte alltid används i praktiken trots att 11 av 13 butiker uppgav att de hade rutiner för kontroll av märkningen vid varumottagningen. Studiens resultat visar att konsumenterna inte alltid kan lita på märkningen av produkter som kakor och choklad, vilket gör det svårare att göra medvetna val av säkra livsmedel

Barnpornografibrott utifrån ett offerperspektiv - En studie av den legala barndefinitionen

Utformningen av den svenska barnpornografibestämmelsen i 16 kap. 10 a § BrB har ifrågasatts alltsedan lagrummets tillkomst år 1980. Legaldefinitionen av barn utgörs av två led, huvudregeln är att den som inte har avslutat sin pubertetsutveckling är att betrakta som barn i lagrummets mening, eller om det av omständigheterna i övrigt framgår att den avbildade personen är under 18 år. Det finns även en bestämmelse i 6 kap. 8 § BrB, förbud mot att utnyttja personer under 18 år för sexuell posering, som är tänkt att fånga upp de fall då en person som är under 18 år har en fullbordad pubertetsutveckling. Jag har studerat barndefinitionen i 16 kap. 10 a § BrB utifrån ett offerper­spektiv, grundat på teorin om det ideala offret samt barnkonventionens barnbegrepp, vilket innebär att barn anses utgöra en särskilt sårbar kategori av offer då barndomen betraktas som en skyddsvärd period av fysisk och psykisk utveckling. Enligt artikel 34 i FN:s konvention om barnets rättigheter skall barn erhålla ett skydd mot sexuellt utnyttjande i form av sexuell exploatering. Med barn avses enligt konventionen samtliga personer under 18 år. Jag har kommit fram till att det föreligger brister utifrån ett offerperspektiv i den förevarande lagstiftningen. Då barndefinitionen bygger på ett pubertetsutvecklingskriterium blir tillämpningen av lagrummet beroende av den fysiska utvecklingen, vilket leder till att endast de unga personer som ser ut som barn erhåller det skydd som samtliga personer under 18 år har rätt till. Bestämmelsen i 6 kap. 8 § BrB, som är tänkt att fylla de luckor som uppstår till följd av pubertetsutvecklingskriteriet vid tillämpningen av 16 kap. 10 a § BrB, skyddar dock inte samtliga barn fullt ut. Bestämmelsen i 6 kap. BrB träffar endast framställningen av pornografiskt material och den kränkningen som barnet utsätts för i samband med denna. Men även övrig befattning såsom spridning och innehav med barnpornografiskt material är kränkande, dels för barnet som utnyttjats i det pornografiska materialet, dels för barn i allmänhet, som enligt förarbetena är rättsskyddssubjekten i 16 kap. 10 a § BrB. Jag anser därmed att barnpornografilagstiftningen bör förändras utifrån ett offerperspektiv. Problematiken med pubertetsutvecklingskriteriet kan undvikas och skyddet mot sexuell exploatering uppnås för samtliga personer under 18 år om det införs en fast åldersgräns i 16 kap. 10 a § BrB. Dock kan inte alla offer för barnpornografibrott identifieras och därför kan en åldersgräns behöva kompletteras med ytterligare rekvisit för att främja en effektiv lagföring. Om lagstiftaren väljer att använda sig av pubertetsutvecklingskriteriet är det viktigt att problematiken kring detta uppmärksammas och diskuteras

Matematik i sällskapsspel för förskolebarn : sällskapsspel som redskap för matematikinlärning

Barns vardag är fylld av matematik, men de behöver hjälp för att bli medvetna om och hur man pratar omkring olika matematiska begrepp. Där har vuxna en betydande roll. Syftet med undersökning är att försöka få en bild av hur pedagoger, barn och föräldrar uppfattar matematiken i sällskapsspelen och hur pedagoger och föräldrar synliggör matematiken i spelen för barnen. Intervjuer har gjorts med pedagoger som arbetar i förskola och förskoleklass. Det har också gjorts intervjuer med barn som går i dessa verksamheter och deras föräldrar. För att se vad som görs i praktiken har pedagoger och barn observerats när de spelar sällskapsspel. Vi redovisar vad tidigare forskning säger om vad som tränas genom att spela sällskapsspel. Resultatet visar att pedagogerna, men framförallt föräldrarna var osäkra på matematiken i sällskapsspel. Trots detta räknade både föräldrar och pedagoger upp många matematiska begrepp vid intervjuerna och pedagogerna gjorde barnen uppmärksamma på olika begrepp vid observationerna. Barnen tycker att man lär sig mycket av spelen, men har svårt att säga något konkret

Långtidsarbetslöshet - En förändring i livet : En socialpsykologisk studie av hur långtidsarbetslösas liv förändras efter en arbetslöshet med fokus på socialt välbefinnande, roll & identitet

Tidigare forskning visar att långtidsarbetslöshet har betydelse för individens livskvalité och att människor utan ett arbete lätt blir till någon som får stå utanför gemenskapen i samhället. Vi önskar i vår C-uppsats att lyfta fram vad som sker i individens liv vid långtidsarbetslöshet, med fokus på hur arbetslösheten ändrat individens sätt att se på sig själv och hur det sociala och arbetsplatsanknutna nätverket förändrats. Vi använde oss av en kvalitativ metod, där vi med en hermeneutisk vetenskaplig ansats genomfört nio stycken semistrukturerade livsvärldsintervjuer. Vi sökte inte efter en absolut sanning, vi intresserade oss av informanternas egna känslor och upplevelser. Deras uttryckta känslor och erfarenheter använde vi sedan för att tolka och analysera vårt material. Resultatet visade att informanternas syn på sig själva drastiskt förändrades efter ett par månader som arbetslösa, de upplevde sig som misslyckade och skämdes över sin situation. I den nya livsituationen var gemenskapen med vänner och familj betydande för hur arbetslösheten hanterades.  Previous research shows that long-term unemployment is important for the individual's quality of life.  But it also shows that people without a job often become someone who is standing outside the community. We wish in our C-ascribed to highlight what´s happening in the individual's life during long-term unemployment, we wish to do this with a focus on how unemployment changed the individual's way of looking at themselves, but also how social and workplace-related network has changed during the unemployment.  We used a qualitative approach, with a hermeneutics scientific method. We conducted nine pieces of semi-structured life-world interviews. We did not seek an absolute truth; we were interested in the informants' own feelings and experiences. We used their expressed feelings and experiences to analyze our material. The results showed that the informants ' views of themselves drastically changed after a couple of months unemployed, they think of  themselves as failures and were ashamed over their situation. In their new life situation friends and family significant for how unemployment could be accepted.

Osynliga offer : En kritisk idéanalys av riksdagsdebatten kring barnpornografilagen.

In this essay, the aim is to empirically and theoretically study the parliamentary debate of the child pornography law. The empirical part is an attempt to discover eventual underlying gender stereotypes in the debate. A text analysis is conducted with material consisting of motions from members of parliament and of protocols from the parliamentary debate. In this material we try to find latent and manifest expressions of gender stereotypes. There are several stereotypes, which effects the argumentation and prejudice of the debate, like stereotypes of the victims, the perpetrators and their characteristics. The general understanding is that the victim is a young girl and the perpetrator is an older man. The male victims are not discussed at all, they are invisible victims. In the theoretical part we combine our empirical results with our theoretical concepts. We analyze the gender stereotypes in relation to postfeminsm, heteronormativity and the theory of the ideal victim. Our conclusion is that the members of the parliament focus on the female victim and the male perpetrator, according to heteronormativity and the theory of the ideal victim. The consequence of the concentration to girls as victims is in our meaning very negative for the young male victims

Surgeons' behaviors and beliefs regarding placebo effects in surgery

Background and purpose — Emerging evidence from sham-controlled trials suggest that surgical treatment entails substantial non-specific treatment effects in addition to specific surgical effects. Yet, information on surgeons’ actual behaviors and beliefs regarding non-specific treatment and placebo effects is scarce. We determined surgeons’ clinical behaviors and attitudes regarding placebo effects. Methods — A national online survey was developed in collaboration with surgeons and administered via an electronic link. Results — All surgical clinics in Sweden were approached and 22% of surgeons participated (n = 105). Surgeons believed it was important for them to interact and build rapport with patients before surgery rather than perform surgery on colleagues’ patients (90%). They endorsed the importance of non-specific treatment effects in surgery generally (90%) and reported that they actively harness non-specific treat- ment effects (97%), including conveying confidence and calm (87%), building a positive interaction (75%), and making eye contact (72%). In communication regarding the likely outcomes of surgery, surgeons emphasized accurate scientific information of benefits/risks (90%) and complete honesty (63%). A majority felt that the improvement after some currently performed surgical procedures might be entirely explained by placebo effects (78%). Surgeons saw benefits with sham-controlled surgery trials, nevertheless, they were reluctant to refer patients to sham controlled trials (46%). Interpretation — Surgeons believe that their words and behaviors are important components of their professional competence. Surgeons saw the patient–physician relation- ship, transparency, and honesty as critical. Understanding the non-specific components of surgery has the potential to improve the way surgical treatment is delivered and lead to better patient outcomes

Balancing health benefits and social sacrifices : a qualitative study of how screening-detected celiac disease impacts adolescents' quality of life

Background Celiac disease often goes undiagnosed. Mass screening might be an option to reduce the public health burden of untreated celiac disease. However, mass screening is still controversial since it is uncertain whether the benefits of early detection outweigh the possible negative consequences. Before implementation of screening programs, the experiences of those being identified as cases should be considered. The aim of our study was to explore how screening-detected celiac disease impacts adolescents' quality of life, as perceived by themselves and their parents. Methods All adolescents (n = 145) with screening-detected celiac disease found in a Swedish screening study, and their parents, were invited to share their experiences in a qualitative follow-up study. In total, we have information on 117 (81%) of the adolescents, either from the adolescents themselves (n = 101) and/or from their parent/s (n = 125). Written narratives were submitted by 91 adolescents and 105 parents. In addition, 14 focus group discussions involving 31 adolescents and 43 parents were conducted. Data was transcribed verbatim and analyzed based on a Grounded Theory framework. Results The screening-detected celiac disease diagnosis had varying impact on quality of life that related both to changes in perceived health and to the adolescents' experiences of living with celiac disease in terms of social sacrifices. Changes in perceived health varied from "healthy as anyone else with no positive change" to "something was wrong and then changed to the better", whereas experiences of living with celiac disease ranged from "not a big deal" to "treatment not worth the price". Perceptions about living with celiac disease and related coping strategies were influenced by contextual factors, such as perceived support from significant others and availability of gluten-free products, and were developed without a direct relation to experiencing changes in perceived health. Conclusions Screening-detected celiac disease has varying impact on adolescents' quality of life, where their perceived change in health has to be balanced against the social sacrifices the diagnosis may cause. This needs to be taken into account in any future suggestion of celiac disease mass screening and in the management of these patients.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p