Loneliness and objectively measured physical capability in middle-aged adults.

Background: Loneliness is associated with poor functional ability in older people. Little is known about this association in the middle-aged. The aim is to investigate if perceived loneliness is associated with lower physical capability among middle-aged men and women and if the associations of loneliness with physical capability interact with socioeconomic position and cohabitation status. Methods: 5224 participants from Copenhagen Aging and Midlife Biobank (CAMB) aged 49-62 years (mean age 54) were included. Handgrip strength (measured by a dynamometer) and maximal number of chair rises in 30 s was recorded. Multivariate linear regression analyses were adjusted for age, occupational social class, cohabitation status, morbidity and personality traits. Results: No association was found between loneliness and physical capability. For example estimates for handgrip strength in 'often' lonely men and women compared with the 'not lonely' were 1.2 kg (95% CI - 0.5;2.9)/1.0 kg (-0.7;2.6). Low occupational social class was associated with poorer physical capability, and living alone was associated with poorer handgrip strength in men [-2.4 kg (95% CI - 3.2;-1.5)] and poorer chair rise test in women [-0.8 rises (95% CI - 1.6;-0.1)]. There was no support for interactions. Conclusion: In contrast to earlier studies among older people, no association between loneliness and physical capability was found in this cohort of middle-aged men and women. Loneliness may not yet have resulted in detectable differences in physical capability in this age group. Further research is needed to clarify if, and at what point in the life course loneliness begins to affect physical capability.

Time trends in alcohol intake in early pregnancy and official recommendations in Denmark, 1998-2013.

INTRODUCTION: In 1999, Danish health authorities modified their recommendation to pregnant women, condoning some alcohol intake. In 2007, the recommendation was changed to one of alcohol abstention. We aimed to assess changes in average alcohol intake (drinks/week) and alcohol binge drinking in early pregnancy from 1998 to 2013 in relation to the changes in official recommendations in 1999 (condoning some intake) and 2007 (abstention). MATERIAL AND METHODS: All Danish-speaking pregnant women attending routine antenatal care at the Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark, between September 1998 and June 2013 were invited to participate. During the study period, 68 395 pregnant women filled in a self-administered questionnaire at gestational week 11 (median). From 1998, questions on binge drinking included data on the number of binge episodes (≥5 drinks on a single occasion), and the timing (gestational week) of these episodes. Additional questions on binge drinking defined as ≥3 drinks on a single occasion were asked separately from 2000. A question assessed the average number of alcohol-containing drinks per week the woman consumed currently at the time of filling in the questionnaire. RESULTS: From 1998 to 2013 the proportion of women reporting no alcohol intake increased from 31.2 to 83.3% (p < 0.001), the main decline occurring between 1998 and 2007. The proportion of binge drinkers decreased (p < 0.001) but remained more stable across the period. CONCLUSIONS: The decline in the proportion of pregnant women consuming alcohol occurred independently of official recommendations. Increasing national and international awareness may partly explain the changes.

Occupational Social Class and Personality Traits in Relation to Leisure-Time Physical Activity Level: Cross-Sectional Results From the Copenhagen Aging and Midlife Biobank.

OBJECTIVE: To investigate separate and combined associations of occupational social class and personality traits with late midlife leisure-time physical activity duration and intensity. METHOD: Cross-sectional data from the Copenhagen Aging and Midlife Biobank ( N = 4,649) were analyzed using linear regression models with leisure-time physical activity (metric equivalence) as outcome. RESULTS: Low versus high occupational social class was associated with 4% (95% confidence interval [CI] = [3%, 5%]) greater leisure-time physical activity duration, but 2% (CI = [1%, 3%]) lower intensity. Each 10-unit increase in extraversion was associated with 5% (CI = [2%, 8%]) greater duration. Intensity increased by each 10-unit increase in conscientiousness (6%, CI = [4%, 7%]), openness (3%, CI = [1%, 4%]), neuroticism (3%, CI = [1%, 4%]), and extraversion (5%, CI = [4%, 7%]). Conscientiousness was positively associated with duration in low, but not in high, occupational social class (interaction p value = .002). DISCUSSION: Higher occupational social class was associated with lower leisure-time physical activity duration, but higher intensity. Extraversion was positively associated with duration and intensity. Conscientiousness, openness, and neuroticism were positively associated with intensity. Overall, interactions were not consistent.

Dopaminergic tone does not influence pain levels during placebo interventions in patients with chronic neuropathic pain.

Placebo effects have been reported in patients with chronic neuropathic pain. Expected pain levels and positive emotions are involved in the observed pain relief, but the underlying neurobiology is largely unknown. Patients with neuropathic pain are highly motivated for pain relief, and as motivational factors such as expectations of reward, as well as pain processing in itself, are related to the dopaminergic system, it can be speculated that dopamine release contributes to placebo effects in neuropathic pain. Nineteen patients with neuropathic pain after thoracic surgery were tested during a placebo intervention consisting of open and hidden applications of the pain-relieving agent lidocaine (2 mL) and no treatment. The dopamine antagonist haloperidol (2 mg) and the agonist levodopa/carbidopa (100/25 mg) were administered to test the involvement of dopamine. Expected pain levels, desire for pain relief, and ongoing and evoked pain were assessed on mechanical visual analog scales (0-10). Significant placebo effects on ongoing (P ≤ 0.003) and evoked (P ≤ 0.002) pain were observed. Expectancy and desire accounted for up to 41.2% and 71.5% of the variance in ongoing and evoked pain, respectively, after the open application of lidocaine. We found no evidence for an effect of haloperidol and levodopa/carbidopa on neuropathic pain levels (P = 0.071-0.963). Dopamine seemed to influence the levels of expectancy and desire, yet there was no evidence for indirect or interaction effects on the placebo effect. This is the first study to suggest that dopamine does not contribute to placebo effects in chronic neuropathic pain.

Impact of childlessness on life and attitudes towards continuation of medically assisted reproduction and/or adoption.

Infertility and fertility treatment have the potential to impact and disrupt a couple's overall life. In order to study the associations between the impact of childlessness on one's life, and men and women's attitudes towards fertility treatment continuation and/or adoption, we analysed data from a one-year follow-up questionnaire in a prospective, longitudinal cohort study of consecutive couples initiating fertility treatment in Denmark. The study comprised 302 couples with no children at baseline and no joint children at one-year follow-up. In total, 71.9% of women and 72.5% of men reported that they wished to continue fertility treatment, while 20.2% of women and 19.2% of men reported that they wished to pursue adoption. The attitudes of nearly 8 in 10 couples were congruent towards further fertility treatments, while nearly 7 in 10 couples were congruent in their attitudes to pursuing adoption. Significantly more men who reported a lower impact of childlessness on their daily life wished to continue fertility treatment, compared with those reporting that childlessness had a greater impact on their life. Among women, significantly more were undecided about whether or not to pursue adoption when reporting a greater impact of childlessness on social life, compared with those reporting a lower impact of their childlessness.

The magnitude of placebo analgesia effects depends on how they are conceptualized.

OBJECTIVE: Placebo effects are usually calculated as the difference between placebo treatments and no treatments. Recently, placebo-like effects have been investigated using open and hidden administrations of active treatments. The aim of the study was to directly compare the two types of placebo effects and examine how they are influenced by personality traits. METHODS: In a within-subject, randomized, blinded, balanced placebo trial design study with 48 healthy volunteers, we compared placebo and placebo-like effects and tested if expectancy, absorption and suggestibility correlated with these effects. Subjects completed the Tellegen Absorption Scale and the Sensory Suggestibility Scale, and pain was induced by injections of hypertonic saline into the masseter muscle. Participants received four injections of hypertonic saline with lidocaine or matching placebo in randomized order: open treatment, hidden treatment, placebo and control. The placebo effect was defined as the difference in pain between the placebo and the control condition and the placebo-like effect as the difference in pain between the open and hidden condition. RESULTS: Placebo effects were significant both in the traditional paradigm: mean placebo effect AUC 1626 mm(2) (95% CI 958-2293) and the open-hidden paradigm: mean placebo-like effect AUC 801 mm(2) (95% CI 134-1469), but there was a significant difference between the magnitude of the two effects (p=0.049). Absorption and suggestibility did not predict the placebo or the placebo-like effect. Estimated expected pain relief correlated with placebo effects but not placebo-like effects. CONCLUSION: The magnitude of placebo effects differs depending on how they are conceptualized and calculated.

Randomised controlled trials may underestimate drug effects: balanced placebo trial design.

BACKGROUND: It is an inherent assumption in randomised controlled trials that the drug effect can be estimated by subtracting the response during placebo from the response during active drug treatment. OBJECTIVE: To test the assumption of additivity. The primary hypothesis was that the total treatment effect is smaller than the sum of the drug effect and the placebo effect. The secondary hypothesis was that non-additivity was most pronounced in participants with large placebo effects. METHODS: We used a within-subject randomised blinded balanced placebo design and included 48 healthy volunteers (50% males), mean (SD) age 23.4 (6.2) years. Experimental pain was induced by injections of hypertonic saline into the masseter muscle. Participants received four injections with hypertonic saline along with lidocaine or matching placebo in randomised order: A: received hypertonic saline/told hypertonic saline; B: received hypertonic saline+lidocaine/told hypertonic saline; C: received hypertonic saline+placebo/told hypertonic saline+pain killer; D: received hypertonic saline+lidocaine/told hypertonic saline+pain killer. The primary outcome measure was the area under the curve (AUC, mm(2)) of pain intensity during injections. RESULTS: There was a significant difference between the sum of the drug effect and the placebo effect (mean AUC 6279 mm(2) (95% CI, 4936-7622)) and the total treatment effect (mean AUC 5455 mm(2) (95% CI, 4585-6324)) (P = 0.049). This difference was larger for participants with large versus small placebo effects (P = 0.015), and the difference correlated significantly with the size of the placebo effect (r = 0.65, P = 0.006). CONCLUSION: Although this study examined placebo effects and not the whole placebo response as in randomised controlled trials, it does suggest that the additivity assumption may be incorrect, and that the estimated drug effects in randomised controlled trials may be underestimated, particularly in studies reporting large placebo responses. The implications for randomised controlled trials and systematic reviews need to be discussed.

Expectations and positive emotional feelings accompany reductions in ongoing and evoked neuropathic pain following placebo interventions.

Research on placebo analgesia and nocebo hyperalgesia has primarily included healthy subjects or acute pain patients, and it is unknown whether these effects can be obtained in ongoing pain in patients with chronic pain caused by an identifiable nerve injury. Eighteen patients with postthoracotomy neuropathic pain were exposed to placebo and nocebo manipulations, in which they received open and hidden administrations of pain-relieving (lidocaine) or pain-inducing (capsaicin) treatment controlled for the natural history of pain. Immediately after the open administration, patients rated their expected pain levels on a mechanical visual analogue scale (M-VAS). They also reported their emotional feelings via a quantitative/qualitative experiential method. Subsequently, patients rated their ongoing pain levels on the M-VAS and underwent quantitative sensory testing of evoked pain (brush, pinprick, area of hyperalgesia, wind-up-like pain). There was a significant placebo effect on both ongoing (P=.009 to .019) and evoked neuropathic pain (P=.0005 to .053). Expected pain levels accounted for significant amounts of the variance in ongoing (53.4%) and evoked pain (up to 34.5%) after the open lidocaine administration. Furthermore, patients reported high levels of positive and low levels of negative emotional feelings in the placebo condition compared with the nocebo condition (P⩽.001). Pain increases during nocebo were nonsignificant (P=.394 to 1.000). To our knowledge, this is the first study to demonstrate placebo effects in ongoing neuropathic pain. It provides further evidence for placebo-induced reduction in hyperalgesia and suggests that patients' expectations coexist with emotional feelings about treatments.