***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Summary Nonspecific placebo factors such as patients ' perceptions of a treatment and expectations toward effect seem to be central to the clinical efficacy of acupuncture analgesia . ABSTRACT It is well known that acupuncture has pain‐relieving effects , but the contribution of specific and especially nonspecific factors to acupuncture analgesia is less clear . One hundred one patients who developed pain of ≥3 on a visual analog scale ( VAS , 0 to 10 ) after third molar surgery were r and omized to receive active acupuncture , placebo acupuncture , or no treatment for 30 min with acupuncture needles with potential for double‐blinding . Patients ' perception of the treatment ( active or placebo ) and expected pain levels ( VAS ) were assessed before and halfway through the treatment . Looking at actual treatment allocation , there was no specific effect of active acupuncture ( P = .240 ) , but there was a large and significant nonspecific effect of placebo acupuncture ( P < .001 ) , which increased over time . Interestingly , however , looking at perceived treatment allocation , there was a significant effect of acupuncture ( P < .001 ) , indicating that patients who believed they received active acupuncture had significantly lower pain levels than those who believed they received placebo acupuncture . Expected pain levels accounted for significant and progressively larger amounts of the variance in pain ratings after both active and placebo acupuncture ( up to 69.8 % ) . This is the first study to show that under optimized blinding conditions , nonspecific factors such as patients ' perception of and expectations toward treatment are central to the efficacy of acupuncture analgesia and that these factors may contribute to self‐reinforcing effects in acupuncture treatment . To obtain an effect of acupuncture in clinical practice , it may therefore be important to incorporate and optimize these factors OBJECTIVE This study investigated the impact of the social modeling of side effects following placebo medication ingestion on the nocebo and placebo effect . It also investigated whether medication br and ing ( br and or generic labeling ) moderated social modeling effects . METHOD Eighty-two university students took part in the study which was purportedly investigating the impact of fast-acting beta-blocker medications ( actually placebos ) on preexamination anxiety . After taking the medication , participants were r and omized to either witness a female confederate report experiencing side effects or no side effects after taking the same medication . Differences in symptom reporting , blood pressure , heart rate , and anxiety were assessed between the social modeling of side effects and no modeling groups . RESULTS Seeing a female confederate report side effects reduced the placebo effect in systolic ( p = .009 ) and diastolic blood pressure ( p = .033 ) . Seeing a female confederate report side effects also increased both total reported symptoms ( mean [ SE ] 7.35 [ .54 ] vs. 5.16 [ 0.53 ] p = .005 ) and symptoms attributed to the medication ( 5.27 [ 0.60 ] vs. 3.04 [ 0.59 ] p = .01 ) , although the effect on symptoms was only seen in female participants . Females who saw the confederate report side effects reported approximately twice the number of symptoms as those in the no modeling group . Social modeling did not affect heart rate or anxiety . Medication br and ing did not influence placebo or nocebo outcomes . CONCLUSIONS The social modeling of symptoms can substantially reduce or eliminate the placebo effect . Viewing a female confederate display symptoms after taking the same medication increases symptom reporting in females Background : Expectancy and modeling have been cited as factors in mass psychogenic illness ( MPI ) , which reportedly affects more women than men . Purpose : The purpose of the study is to assess the effects of expectancy and modeling in a controlled laboratory analogue of MPI . Methods : Students were r and omly assigned to inhale or not inhale an inert placebo described as a suspected environmental toxin that had been linked to four symptoms typical of reported instances of MPI . Half of the students observed a female confederate inhale the substance and subsequently display the specified symptoms . Results : Students who inhaled the placebo reported greater increases in symptoms , and the increase was significantly greater for the specified symptoms than for other symptoms . Observation of the confederate displaying symptoms increased specified symptoms significantly among women but not among men . Changes in reported symptoms were significantly associated with changes in unobtrusively observed behavior . Conclusions : Symptoms typical of clinical reports of MPI can be induced by manipulating response expectancies , and the effects are specific rather than generalized . Among women , this effect is enhanced by observing another participant ( who in this study is also female ) display symptoms . This suggests that the preponderance of women showing symptoms in outbreaks of MPI may be due to gender-linked differences in the effects of modeling on psychogenic symptoms OBJECTIVES : Multiple chemical sensitivity is a poorly understood syndrome in which various symptoms are triggered by chemically unrelated , but often odorous substances , at doses below those known to be harmful . This study focuses on the process of pavlovian acquisition and extinction of somatic symptoms triggered by odours . METHODS : Diluted ammonia and butyric acid were odorous conditioned stimuli ( CS ) . The unconditioned stimulus ( US ) was 7.4 % CO2 enriched air . One odour ( CS+ ) was presented together with the US for 2 minutes ( CS+ trial ) , and the other odour ( CS- ) was presented with air ( CS-trial ) . Three CS+ and three CS-exposures were run in a semi-r and omised order ; this as the acquisition ( conditioning ) phase . To test the effect of the conditioning , each subject then had one CS+ only -- that is , CS+ without CO2 - - and one CS- test exposure . Next , half the subjects ( n = 32 ) received five additional CS+ only exposures ( extinction group ) , while the other half received five exposures to breathing air ( wait group ) . Finally , all subjects got one CS+ only test exposure to test the effect of the extinction . Ventilatory responses were measured during and somatic symptoms after each exposure . RESULTS : More symptoms were reported upon exposure to CS+ only than to CS-odours , regardless of the odour type . Altered respiratory rate was only found when ammonia was CS+ . Five extinction trials were sufficient to reduce the level of acquired symptoms . CONCLUSION : Subjects can acquire somatic symptoms and altered respiratory behaviour in response to harmless , but odorous chemical substances , if these odours have been associated with a physiological challenge that originally had caused these symptoms . The conditioned symptoms can subsequently be reduced in an extinction procedure . The study further supports the plausibility of a pavlovian conditioning hypothesis to explain the pathogenesis of MCS Abstract Medical treatment is usually accompanied by a warning about potential side effects . While constituting an important component of informed consent , these warnings may themselves contribute to side effects via the placebo effect . We tested this possibility using a 2 × 2 between-subjects design . Under the guise of a trial of a new hypnotic , 91 undergraduates experiencing difficulty sleeping were allocated to receive a warning about a target side effect ( either increase or decrease in appetite , counterbalanced ) or no warning and then to receive placebo treatment or no treatment for one week . Placebo treatment led to significantly better sleep on almost all self-reported outcomes , suggesting a placebo effect for reported sleep difficulty . Actigraphy recordings were unaffected by treatment . There was a clear effect of the warning in that placebo treated participants who were warned about side effects were much more likely to report the target side effect than those not warned about side effects . Implication s for clinical practice are discussed The nocebo effect is the onset of untoward reactions following the administration of an indifferent substance . The oral challenge with alternative drugs plays a central role in the management of drug allergy and the use of inert substances is part of this procedure . We evaluated the occurrence and clinical characteristics of nocebo effect in patients with adverse drug reactions . Six hundred patients , seen in three different centres ( Genoa , Naples and Verona ) with a history of reactions to drugs , underwent a blind oral challenge with the administration of an indifferent substance and active drugs . The administration of an inert substance provoked untoward reactions in 54 patients ( 27 % ) in Verona , 60 ( 30 % ) in Naples and 48 ( 24 % ) in Genoa . The overall occurrence of nocebo effect was 27 % . The majority of reactions were subjective symptoms ( itching , malaise , headache etc ) , perceived as troublesome by all subjects . The occurrence was significantly higher in women than in men . Our data , collected in a large population , confirm that the nocebo effect occurs frequently in clinical practice . In managing adverse drug reactions through oral challenge the nocebo effect is m and atory to recognize false positive responses Objective Generic medications are associated with reduced perceived effectiveness , increased perceived adverse effects , and increased rates of nonadherence compared with br and -name medications . This study examined the effect of an apparent medication formulation change on subjective and objective measures of medication effectiveness and medication side effects . Methods Sixty-two university students participated in a study purportedly testing the effectiveness of fast-acting & bgr;-blocker medications in reducing preexamination anxiety . All tablets were placebos . In session 1 , all participants received a yellow tablet ( “ Betaprol ” ) . In session 2 , participants were r and omly allocated to receive Betaprol ( no change condition ) or a white tablet labeled either as “ Novaprol ” ( br and ed change condition ) or “ Generic ” ( generic change condition ) . Blood pressure and state anxiety were measured before and after tablet ingestion . Side effects attributed to medication were assessed . Results The no change group showed significantly greater decreases in systolic blood pressure ( mean [ M ] [ st and ard deviation ] = −7.72 mm Hg , st and ard error [ SE ] = 1.45 ) than the br and ed change ( M = −2.75 mm Hg , SE = 1.44 , p = .02 ) and generic change ( M = −3.26 mm Hg , SE = 1.45 , p = .03 ) groups . The no-change group showed significantly greater decreases in state anxiety ( M = −1.53 , SE = 0.33 ) than the br and ed change ( M = −0.50 , SE = 0.33 , p = .03 ) and generic change ( M = −0.52 , SE = 0.33 , p = .04 ) groups . Significantly more side effects were attributed to the medication in the generic change ( M = 1.83 , SE = 0.23 ) ( but not the br and ed change ) condition when compared with the no change condition ( M = 0.87 , SE = 0.31 , p = .03 ) . Conclusions Medication formulation change , particularly to generic medication , seems to be associated with reduced subjective and objective measures of medication effectiveness and increased side effects Caffeine consumption , a ubiquitous cultural phenomenon with significant health implication s may be governed by some of the same principles which affect other drug use [ 1 ] . We hypothesized that pharmacological and expectancy effects may be two of those principles . A balanced placebo design was used with 100 male undergraduates to separate caffeine 's active drug effects from the expectancy of having consumed caffeine on mood , performance , and physiological measures . The manipulation of expectancies was highly effective on subjects ' judgments of caffeine dosage , regardless of actual caffeine content . As predicted , expectancy set and caffeine content appeared equally powerful , and worked additively , to affect subjects ' ratings of how much the coffee influenced their mood and performance . Main effects on systolic and diastolic blood pressure , pulse rate , and a fatigue measure were found for caffeine vs. no caffeine groups only . Additional increases in diastolic blood pressure for smokers were noted within the caffeine-receiving conditions . Results are discussed with heuristic and health implication Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Abstract . Rationale : To test the classical conditioning and expectancy theories of placebo effects . Objective : Two experiments investigated whether administration of caffeine-associated stimuli elicited conditioned arousal , and whether information that a drink contained or did not contain caffeine modulated arousal . Method : Experiment 1 ( n=21 ) used a 2 Caffeine ( 0 and 2 mg/kg ) × 2 Solution ( Coffee , Juice ) × 2 Information ( Told caffeine , Told not-caffeine ) within-subjects design . Experiment 2 ( n=48 ) used a 2 Solution ( Coffee , Orange juice ) × 3 Information ( Told caffeine , Told not-caffeine , No information ) between-subjects design . Indexes of arousal were skin conductance responses and levels , startle eyeblink reflexes , cardiovascular measures , and the Bond and Lader 1974 mood scale . Results : Caffeine-associated stimuli increased alertness , contentedness and skin conductance levels , and information that the drink contained caffeine decreased calmness in Experiment 1 . However , unexpected information about the caffeine content of the drink , and the order of the conditions , could have masked some effects of the experimental manipulations . Experiment 2 followed up this hypothesis . The results showed a conditioned increase in startle eyeblink reflexes , and that caffeine-associated stimuli together with information that the drink contained caffeine increased contentedness . Conclusions : Caffeine-associated stimuli increased arousal , and information about the content of the drink modulated arousal in the direction indicated by the information . Thus , both the classical conditioning and expectancy theories of placebo effects received support , and placebo effects were strongest when both conditioned responses and expectancy-based responses acted in the same 
    Output:
    
The strongest predictors of nocebo effects were a higher perceived dose of exposure , explicit suggestions that the exposure triggers arousal or symptoms , observing people experiencing symptoms from the exposure , and higher expectations of symptoms .
CONCLUSIONS To reduce nocebo induced symptoms associated with medication or other interventions clinicians could reduce expectations of symptoms , limit suggestions of symptoms , correct unrealistic dose perceptions , and reduce exposure to people experiencing side effects .