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1.  Persistent pain in a community-based sample of children and adolescents: Sex differences in psychological constructs 
The prevalence of persistent and recurrent pain among children and adolescents has important economic, social and psychological repercussions. The impact of chronic pain in children extends beyond the affected individuals – more than one-third of parents of children with pain report clinically significant levels of stress and depression. Although many pain-related psychological factors have been examined in chronic pediatric pain populations, much of that research involved clinical samples. Community-based research, however, is necessary to uncover the way pain is experienced by youth, regardless of whether treatment is sought or is available. This study aimed to ascertain the lifetime prevalence of pediatric pain in a Canadian community-based sample, and to explore age and sex differences in children who report persistent pain and those who do not with respect to several constructs believed to play important roles in the development and maintenance of persistent pain.
BACKGROUND:
Very few studies have investigated the psychological factors associated with the pain experiences of children and adolescents in community samples.
OBJECTIVES:
To examine the lifetime prevalence of, and psychological variables associated with, persistent pain in a community sample of children and adolescents, and to explore differences according to sex, age and pain history.
METHODS:
Participants completed the Childhood Anxiety Sensitivity Index (CASI), the Child Pain Anxiety Symptoms Scale (CPASS), the Multidimensional Anxiety Scale for Children-10 (MASC-10), the Pain Catastrophizing Scale for Children (PCS-C) and a pain history questionnaire that assessed chronicity and pain frequency. After research ethics board approval, informed consent/assent was obtained from 1022 individuals recruited to participate in a study conducted at the Ontario Science Centre (Toronto, Ontario).
RESULTS:
Of the 1006 participants (54% female, mean [± SD] age 11.6±2.7 years) who provided complete data, 27% reported having experienced pain that lasted for three months or longer. A 2×2×2 (pain history, age and sex) multivariate ANOVA was conducted, with the total scores on the CASI, the CPASS, the MASC-10 and the PCS-C as dependent variables. Girls with a history of persistent pain expressed higher levels of anxiety sensitivity (P<0.001) and pain catastrophizing (P<0.001) than both girls without a pain history and boys regardless of pain history. This same pattern of results was found for anxiety and pain anxiety in the older, but not the younger, age group.
CONCLUSIONS:
Boys and girls appear to differ in terms of how age and pain history relate to the expression of pain-related psychological variables. Given the prevalence of persistent pain found in the study, more research is needed regarding the developmental implications of persistent pain in childhood and adolescence.
PMCID: PMC3206778  PMID: 22059200
Children; Persistent pain; Psychosocial factors; Sex differences
2.  Parent and child anxiety sensitivity: Relationship to children’s experimental pain responsivity 
Anxiety sensitivity (AS) or fear of anxiety sensations has been linked to childhood learning history for somatic symptoms, suggesting that parental AS may impact children’s responses to pain. Using structural equation modeling (SEM), we tested a conceptual model in which parent AS predicted child AS, which in turn predicted a hypothesized latent construct consisting of children’s pain intensity ratings for three laboratory pain tasks (cold pressor, thermal heat and pressure). This conceptual model was tested in 211 non-clinical parent-child pairs (104 girls, mean age = 12.4 years; 178 mothers). Our model was supported in girls only indicating that the sex of the child moderated the hypothesized relationships. Thus, parent AS was related to child laboratory pain intensity via its contribution to child AS in girls but not in boys. In girls, 42% of the effect of parent AS on laboratory pain intensity was explained via child AS. In boys, there was no clear link between parent AS and child AS, although child AS was predictive of experimental pain intensity across sex. Our results are consistent with the notion that parent AS may operate via healthy girls’ own fear of anxiety symptoms to influence their responses to laboratory pain stimuli.
Perspective-The present study highlights sex differences in the links among parent and child anxiety sensitivity (AS; fear of anxiety sensations) and children’s experimental pain responses. Among girls, childhood learning history related to somatic symptoms may be a particularly salient factor in the development of AS and pain responsivity.
doi:10.1016/j.jpain.2005.12.004
PMCID: PMC1540407  PMID: 16632321
anxiety sensitivity; laboratory pain; children; adolescents; parent; sex differences
3.  Anxiety sensitivity, fear of pain and pain-related disability in children and adolescents with chronic pain 
BACKGROUND:
Converging lines of evidence suggest that anxiety sensitivity and fear of pain may be important vulnerability factors in the development of avoidance behaviours and disability in adults with chronic pain. However, these factors have not been evaluated in children with chronic pain.
OBJECTIVES:
To examine the relationships among anxiety sensitivity, fear of pain and pain-related disability in children and adolescents with chronic pain.
METHODS:
An interview and five questionnaires (Childhood Anxiety Sensitivity Index, Pain Anxiety Symptoms Scale, Functional Disability Inventory, Multidimensional Anxiety Scale for Children, and Reynolds Child or Adolescent Depression Scale) were administered to 21 children and adolescents eight to 17 years of age (mean ± SD 14.24±2.21 years) who continued to experience pain an average of three years after discharge from a specialized pain clinic for children.
RESULTS:
Anxiety sensitivity accounted for 38.6% of the variance in fear of pain (F[1,20]=11.30; P=0.003) and fear of pain accounted for 39.9% of the variance in pain-related disability (F[1,20]=11.95; P=0.003), but anxiety sensitivity was not significantly related to pain disability (R2=0.09; P>0.05).
CONCLUSIONS:
These findings indicate that children with high levels of anxiety sensitivity had a higher fear of pain, which, in turn, was linked to increased pain disability. The results of this study suggest that anxiety sensitivity and fear of pain may play important and distinct roles in the processes that maintain chronic pain and pain-related disability in children.
PMCID: PMC2670737  PMID: 18080045
Anxiety sensitivity; Children; Chronic pain; Disability; Fear of pain
4.  Relationships among Anxious Symptomatology, Anxiety Sensitivity and Laboratory Pain Responsivity in Children 
Cognitive behaviour therapy  2006;35(4):207-215.
Existing laboratory-based research in adult samples has suggested that anxiety sensitivity (AS) increases an individual’s propensity to experience pain-related anxiety which in turn enhances pain responsivity. Such relationships have not been examined in younger populations. Thus, the present study used structural equation modeling (SEM) to test a conceptual model in which AS would evidence an indirect relationship with pain intensity via its contribution to state-specific anticipatory anxiety in relation to a variety of laboratory pain tasks (cold pressor, thermal heat, and pressure pain) in 234 healthy children (116 girls; mean age = 12.6 years, range = 8–18 years). The model further hypothesized that existing anxious symptomatology would demonstrate a direct relationship with pain intensity. Results of the SEM supported the proposed conceptual model with the total indirect effect of AS accounting for 29% of the variance in laboratory pain intensity via its effects on pain-related anticipatory anxiety. AS did not however, evidence a direct relationship with pain intensity. Anxious symptomatology on the other hand, demonstrated a significant direct effect on pain intensity, accounting for 15% of variance. The combined effects of AS, anxiety symptoms, and anticipatory anxiety together explained 62% of the variance in pain intensity. These relationships did not differ for boys and girls indicating no moderating effect of sex in the proposed model. The present results support the potential benefit of assessing both AS and anxiety symptoms in children prior to undergoing painful stimulation.
doi:10.1080/16506070600898272
PMCID: PMC1783843  PMID: 17189238
children; adolescents; anxiety; anxiety sensitivity; laboratory pain; experimental pain; pain intensity
5.  Anxiety sensitivity and health-related quality of life in children with chronic pain 
Anxiety sensitivity (AS), or the fear of anxiety sensations has been shown to independently predict poorer health-related quality of life (HRQOL) in adults with chronic pain. Specifically, AS was found to contribute to decrements in psychological well-being and social functioning but not to decrements in physical functioning. Existing studies have not examined the relationship between AS and HRQOL in children with chronic pain. The present study used multivariate regression analysis to test the association between AS and self-reported HRQOL in 87 children (62 girls; mean age = 14.4 years ± 2.3) presenting for treatment at a tertiary, multidisciplinary clinic specializing in pediatric chronic pain. After controlling for key sociodemographic and pain-related characteristics, higher AS was associated with poorer perceived general and mental health, greater impairment in family activities, lower self-esteem, increased behavior problems, and more social/academic limitations due to emotional problems. AS accounted for 4% – 28% of incremental variance in these HRQOL domains above and beyond the demographic and pain-related variables. However, AS was not significantly associated with physical functioning or with academic/social limitations due to physical health. Additional research is required to delineate possible mechanisms by which AS may influence certain aspects of children's HRQOL but not others.
Perspective
The present findings support the evaluation of AS in pediatric chronic pain patients as part of a comprehensive assessment battery. The links between AS and multiple HRQOL domains suggests that treatment components aimed at reducing AS may lead to enhanced psychosocial well-being in children with chronic pain.
doi:10.1016/j.jpain.2007.05.011
PMCID: PMC2084210  PMID: 17613277
health-related quality of life; anxiety sensitivity; children; chronic pain; pain-related anxiety; functional impairment
6.  Sex Differences in the Association Between Cortisol Concentrations and Laboratory Pain Responses in Healthy Children 
Gender medicine  2009;6(Suppl 2):193-207.
Background
Research in adult populations has highlighted sex differences in cortisol concentrations and laboratory pain responses, with men exhibiting higher cortisol concentrations and reduced pain responses compared with women. Yet, less is known about the relationship of cortisol concentrations to pain in children.
Objective
This study examined associations between sex, cortisol, and pain responses to laboratory pain tasks in children.
Methods
Salivary cortisol samples from subjects aged 8 to 18 years were obtained at baseline after entering the laboratory (SCb), after the completion of all pain tasks (SC1), and at the end of the session (SC2), 20 minutes later. Blood cortisol samples were also taken after completion of the pain tasks (BC1) and at the end of the session (BC2), 20 minutes later. Subjects completed 3 counterbalanced laboratory pain tasks: pressure, heat, and cold pressor tasks. Pain measures included pain tolerance, and self-reported pain intensity and unpleasantness for all 3 tasks.
Results
The study included 235 healthy children and adolescents (119 boys, 116 girls; mean age, 12.7 years; range, 8–18 years; 109 [46.4%] were in early puberty; 94 [40.0%] white). Salivary and blood cortisol levels were highly correlated with each other. Salivary cortisol levels for the total sample and for boys and girls declined significantly from SCb to SC1 (P < 0.01), although there were no significant changes from SC1 to SC2. No significant sex differences in salivary or blood cortisol levels were evident at any assessment point. Separate examination of the cortisol–laboratory pain response relationships by sex (controlling for age and time of day) suggested different sex-specific patterns. Higher cortisol levels were associated with lower pain reactivity (ie, increased pressure tolerance) among boys compared with girls at SC1, SC2, and BC1 (SC1: r = 0.338, P = 0.003; SC2: r = 0.271, P = 0.020; and BC1: r = 0.261, P = 0.026). However, higher cortisol levels were related to higher pain response (ie, increased cold intensity [BC2: r = 0.229, P = 0.048] and unpleasantness [BC1: r = 0.237, P = 0.041]) in girls compared with boys.
Conclusions
These findings suggest important sex differences in cortisol–pain relationships in children and adolescents. Cortisol levels were positively associated with increased pain tolerance in boys and increased pain sensitivity in girls.
doi:10.1016/j.genm.2009.03.001
PMCID: PMC3486740  PMID: 19406369
pain; children; cortisol; sex differences
7.  Chronic pain and pain-related disability across psychiatric disorders in a clinical adolescent sample 
BMC Psychiatry  2013;13:272.
Background
People who suffer from psychiatric disorders are burdened with a high prevalence of chronic illnesses and pain, but evidence on pain prevalence among adolescents with psychiatric disorders is scarce. The aim of this study was to investigate the frequency and location of self-reported chronic pain and pain-related disability in adolescent psychiatric patients.
Methods
This study was part of the larger Health Survey administered at the Department of Child and Adolescent Psychiatry (CAP) at St. Olav’s University Hospital, in Trondheim, Norway. All patients aged 13–18 years who visited the CAP clinic at least once between February 15, 2009 and February 15, 2011 were invited to participate. A total of 717 (43.5% of eligible/invited patients) participated; of these, 566 were diagnosed with one or more psychiatric disorders. The adolescents completed a questionnaire, which included questions about pain and pain-related disability. Clinical diagnoses were classified by a clinician according to International Statistical Classification of Diseases and Related Health Problems, 10th revision criteria.
Results
In adolescents with psychiatric disorders, 70.4% reported chronic pain, and 37.3% experienced chronic pain in three or more locations (multisite pain). Chronic musculoskeletal pain was the most prevalent type of pain (57.7%). Pain-related disability was found in 22.2% of the sample. The frequency of chronic pain and multisite pain increased with age, and girls reported a higher frequency of chronic pain, multisite pain and pain-related disability than boys did. There was an increased risk of chronic pain among adolescents with mood or anxiety disorders versus those with hyperkinetic disorders, yet this was not present after adjusting for sex. Comorbidity between hyperkinetic and mood or anxiety disorders involved an increased risk of pain-related disability.
Conclusions
In this study, seven out of 10 adolescents with psychiatric disorders reported chronic pain. These findings indicate the importance of early detection of chronic pain in adolescents with psychiatric disorders, to provide targeted treatment and reduce poor long-term outcomes.
doi:10.1186/1471-244X-13-272
PMCID: PMC3853574  PMID: 24139217
Chronic pain; Disability; Prevalence; Psychiatric disorders; Adolescents
8.  Characteristics of highly impaired children with severe chronic pain: a 5-year retrospective study on 2249 pediatric pain patients 
BMC Pediatrics  2012;12:54.
Background
Prevalence of pain as a recurrent symptom in children is known to be high, but little is known about children with high impairment from chronic pain seeking specialized treatment. The purpose of this study was the precise description of children with high impairment from chronic pain referred to the German Paediatric Pain Centre over a 5-year period.
Methods
Demographic variables, pain characteristics and psychometric measures were assessed at the first evaluation. Subgroup analysis for sex, age and pain location was conducted and multivariate logistic regression applied to identify parameters associated with extremely high impairment.
Results
The retrospective study consisted of 2249 children assessed at the first evaluation. Tension type headache (48%), migraine (43%) and functional abdominal pain (11%) were the most common diagnoses with a high rate of co-occurrence; 18% had some form of musculoskeletal pain disease. Irrespective of pain location, chronic pain disorder with somatic and psychological factors was diagnosed frequently (43%). 55% of the children suffered from more than one distinct pain diagnosis. Clinically significant depression and general anxiety scores were expressed by 24% and 19% of the patients, respectively. Girls over the age of 13 were more likely to seek tertiary treatment compared to boys. Nearly half of children suffered from daily or constant pain with a mean pain value of 6/10. Extremely high pain-related impairment, operationalized as a comprehensive measure of pain duration, frequency, intensity, pain-related school absence and disability, was associated with older age, multiple locations of pain, increased depression and prior hospital stays. 43% of the children taking analgesics had no indication for pharmacological treatment.
Conclusion
Children with chronic pain are a diagnostic and therapeutic challenge as they often have two or more different pain diagnoses, are prone to misuse of analgesics and are severely impaired. They are at increased risk for developmental stagnation. Adequate treatment and referral are essential to interrupt progression of the chronic pain process into adulthood.
doi:10.1186/1471-2431-12-54
PMCID: PMC3404028  PMID: 22591492
Children; Chronic pain; Impairment; Risk factors; Pediatric
9.  Perception of venipuncture pain in children suffering from chronic diseases 
BMC Research Notes  2014;7(1):735.
Background
Venipuncture pain in children results from a variety of co-factors which increase the intensity of the nociceptive stimulus. Among them, anticipatory anxiety plays an important role. Children with chronic diseases undergo invasive procedures and venipuncture more often than other children. Some healthcare professionals still believe that children who are repeatedly exposed to painful procedures, such as children with chronic diseases, gradually increase their pain tolerance and that, as a result, they have a higher pain threshold than children with no chronic diseases. The purpose of this study was to assess whether a difference exists in the perception of venipuncture pain between children with chronic diseases and children with no previous health problems nor experience of venipuncture.
Methods
A cross-sectional study was carried out using the Wong and numeric pain scales and the Observational Scale of Behavioral Distress (OSBD) for the assessment of behavioral distress. A group of children with chronic diseases and a group of children with no previous health problems nor experience of venipuncture, aged 4 to 12 years, both boys and girls, were observed during a standardized venipuncture procedure.
Results
The study included 230 children in total: 82 of them suffered from chronic diseases and had already experienced venipuncture at least once, while the remaining 148 children had no previous experience of venipuncture. The children with chronic diseases reported more pain (median pain score of 8 on the Wong or numeric scales,) and showed more signs of behavioral distress (median score of 27 on the OSBD) than non-chronic children (median pain score of 2 on the Wong/numeric scales, p = 0.00001; median OSBD score 5, p = 0.00001).
Conclusions
Our study suggests that children with chronic diseases have a lower pain threshold than children of the same sex and age who experience venipuncture for the first time.
doi:10.1186/1756-0500-7-735
PMCID: PMC4210598  PMID: 25326685
10.  Relationship of Salivary Alpha Amylase and Cortisol to Social Anxiety in Healthy Children Undergoing Laboratory Pain Tasks 
Objective
Salivary alpha amylase (sAA) has been shown to be a sensitive and reliable marker of the autonomic nervous system (ANS) response to stress. A link between sAA, cortisol, and social/evaluative stress has been established in youth, but little is known about these relationships in response to other stressors in children, and how social anxiety might moderate these relationships. The current study explored the associations among sAA and salivary cortisol responses to laboratory pain tasks and self-reported social anxiety symptoms in a sample of healthy children.
Method
Two hundred thirty-one children (114 girls; 49.4%) with a mean age 12.68 years (SD=3.0; range 7–18) participated in the study. Participants completed self-report questionnaires prior to undergoing a series of laboratory pain tasks involving cold, pressure, and heat pain. Saliva samples were collected upon arrival to the laboratory (pre-task), following the completion of the pain tasks (post-task1), and 20 minutes after the completion of the pain tasks (post-task2).
Results
Demographic factors (age, sex, pubertal stage) did not predict either sAA or cortisol levels. However, children reporting higher levels of social anxiety demonstrated significantly higher sAA but not cortisol levels across three salivary collection times, compared to children reporting lower levels of social anxiety. Further, it does not appear that reduced state levels of anxiety before or during the tasks buffer this relationship.
Conclusion
These data highlight the possibility of identifying biomarkers of stress that are consistent across time and developmental stage. sAA appears to be a marker of stress response in children with self-reported social anxiety. There may also be a potentially unique relationship of sAA to stress in this population. In addition, sAA may reflect stable individual differences in levels of ANS arousal and may be a useful biomarker for identifying children at risk for stress.
doi:10.4172/jcalb.1000129
PMCID: PMC4267054  PMID: 25525630
Alpha amylase; Cortisol; Social anxiety; Anxiety; stress; Children; Youth; Pain
11.  Child Mortality Estimation: Estimating Sex Differences in Childhood Mortality since the 1970s 
PLoS Medicine  2012;9(8):e1001287.
Cheryl Sawyer uses new methods to generate estimates of sex differences in child mortality which can be used to pinpoint areas where these differences in mortality merit closer examination.
Introduction
Producing estimates of infant (under age 1 y), child (age 1–4 y), and under-five (under age 5 y) mortality rates disaggregated by sex is complicated by problems with data quality and availability. Interpretation of sex differences requires nuanced analysis: girls have a biological advantage against many causes of death that may be eroded if they are disadvantaged in access to resources. Earlier studies found that girls in some regions were not experiencing the survival advantage expected at given levels of mortality. In this paper I generate new estimates of sex differences for the 1970s to the 2000s.
Methods and Findings
Simple fitting methods were applied to male-to-female ratios of infant and under-five mortality rates from vital registration, surveys, and censuses. The sex ratio estimates were used to disaggregate published series of both-sexes mortality rates that were based on a larger number of sources. In many developing countries, I found that sex ratios of mortality have changed in the same direction as historically occurred in developed countries, but typically had a lower degree of female advantage for a given level of mortality. Regional average sex ratios weighted by numbers of births were found to be highly influenced by China and India, the only countries where both infant mortality and overall under-five mortality were estimated to be higher for girls than for boys in the 2000s. For the less developed regions (comprising Africa, Asia excluding Japan, Latin America/Caribbean, and Oceania excluding Australia and New Zealand), on average, boys' under-five mortality in the 2000s was about 2% higher than girls'. A number of countries were found to still experience higher mortality for girls than boys in the 1–4-y age group, with concentrations in southern Asia, northern Africa/western Asia, and western Africa. In the more developed regions (comprising Europe, northern America, Japan, Australia, and New Zealand), I found that the sex ratio of infant mortality peaked in the 1970s or 1980s and declined thereafter.
Conclusions
The methods developed here pinpoint regions and countries where sex differences in mortality merit closer examination to ensure that both sexes are sharing equally in access to health resources. Further study of the distribution of causes of death in different settings will aid the interpretation of differences in survival for boys and girls.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
In 2000, world leaders agreed to eradicate extreme poverty by 2015. To help track progress towards this global commitment, eight Millennium Development Goals (MDGs) were set. MDG 4, which aims to reduce child mortality, calls for a reduction in under-five mortality (the number of children who die before their fifth birthday) to a third of its 1990 level of 12 million by 2015. The under-five mortality rate is also denoted in the literature as U5MR and 5q0. Progress towards MDG 4 has been substantial, but with only three years left to reach it, efforts to strengthen child survival programs are intensifying. Reliable estimates of trends in childhood mortality are pivotal to these efforts. So, since 2004, the United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) has used statistical regression models to produce estimates of trends in under-five mortality and infant mortality (death before age one year) from data about childbearing and child survival collected by vital registration systems (records of all births and deaths), household surveys, and censuses.
Why Was This Study Done?
In addition to estimates of overall childhood mortality trends, information about sex-specific childhood mortality trends is desirable to monitor progress towards MDG 4, although the interpretation of trends in the relative mortality of girls and boys is not straightforward. Newborn girls survive better than newborn boys because they are less vulnerable to birth complications and infections and have fewer inherited abnormalities. Thus, the ratio of infant mortality among boys to infant mortality among girls is greater than one, provided both sexes have equal access to food and medical care. Beyond early infancy, girls and boys are similarly vulnerable to infections, so the sex ratio of deaths in the 1–4-year age group is generally lower than that of infant mortality. Notably, as living conditions improve in developing countries, infectious diseases become less important as causes of death. Thus, in the absence of sex-specific differences in the treatment of children, the sex ratio of childhood mortality is expected be greater than one and to increase as overall under-five mortality rates in developing countries decrease. In this study, the researcher evaluated national and regional changes in the sex ratios of childhood mortality since the 1970s to investigate whether girls and boys have equal access to medical care and other resources.
What Did the Researcher Do and Find?
The researcher developed new statistical fitting methods to estimate trends in the sex ratio of mortality for infants and young children for individual countries and world regions. When considering individual countries, the researcher found that for 92 countries in less developed regions, the median sex ratio of under-five mortality increased between the 1970s and the 2000s, in line with the expected changes just described. However, the average sex ratio of under-five mortality for less developed regions, weighted according to the number of births in each country, did not increase between the 1970s and 2000s, at which time the average under-five mortality rate of boys was about 2% higher than that of girls. This discrepancy resulted from India and China—the two most populous developing countries—having sex ratios for both infant and under-five mortality that remained constant or declined over the study period and were below one in the 2000s, a result that indicates excess female mortality. In China, for example, infant mortality was found to be 12% higher for boys than for girls in the 1970s, but 24% lower for boys than for girls in the 2000s. Finally, although in the less developed regions (excluding India and China) girls went from having a slight survival disadvantage at ages 1–4 years in the 1970s, on average, to having a slight advantage in the 2000s, girls remained more likely to die than boys in this age group in several Asian and African countries.
What Do These Findings Mean?
Although the quality of the available data is likely to affect the accuracy of these findings, in most developing countries the ratio of male to female under-five mortality has increased since the 1970s, in parallel with the decrease in overall childhood mortality. Notably, however, in a number of developing countries—including several each in sub-Saharan Africa, northern Africa/western Asia, and southern Asia—girls have higher mortality than boys at ages 1–4 years, and in India and China girls have higher mortality in infancy. Thus, girls are benefitting less than boys from the overall decline in childhood mortality in India, China, and some other developing countries. Further studies are needed to determine the underlying reasons for this observation. Nevertheless, the methods developed here to estimate trends in sex-specific childhood mortality pinpoint countries and regions where greater efforts should be made to ensure that both sexes have equal access to health care and other important resources during early life.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001287.
This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine
The United Nations Childrens Fund works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the United Nations Inter-agency Group for Child Mortality Estimation; the 2011 UN IGME report Levels & Trends in Child Mortality is available
The World Health Organization also has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages)
Further information about the Millennium Development Goals is available
A 2011 report by the United Nations Department of Economic and Social Affairs entitled Sex Differentials in Childhood Mortality is available
doi:10.1371/journal.pmed.1001287
PMCID: PMC3429399  PMID: 22952433
12.  Relationship of child perceptions of maternal pain to children's laboratory and non-laboratory pain 
Previous research has established links between parent and child pain. Yet little is known about sex-specific parent-child pain relationships in a non-clinical population. A sample of 186 children aged 8–18 years (49% female) provided information on maternal and self bodily-pain, assessed by asking children about the presence and location of bodily pain experienced. Children also completed three laboratory pain tasks and reported on cold pressor pain intensity, pressure pain intensity and heat pain intensity. The presence of child-reported maternal pain was consistently correlated with daughters’ bodily and laboratory pain, but not with sons’ pain in bivariate analyses. Multivariate analyses controlling for child age and maternal psychological distress indicated that children of mothers with bodily pain reported more total bodily pain sites as well as greater pressure and cold pain intensity, relative to children of mothers without bodily pain. For cold pain intensity, these results differed for boys vs. girls, in that daughters reporting maternal pain evidenced significantly higher cold pain intensity compared to daughters not reporting maternal pain. No such differences were found for boys. The findings suggest that children’s perceptions of maternal pain may play a role in influencing children’s own experience of pain and that maternal pain models may affect boys and girls differently.
PMCID: PMC2642517  PMID: 18592057
pain; sex differences; social learning; children
13.  Sex differences in the relationship between maternal fear of pain and children’s conditioned pain modulation 
Journal of Pain Research  2013;6:231-238.
Background
Parental behaviors, emotions, and cognitions are known to influence children’s response to pain. However, prior work has not tested the association between maternal psychological factors and children’s responses to a conditioned pain modulation (CPM) task. CPM refers to the reduction in perceived pain intensity for a test stimulus following application of a conditioning stimulus to a remote area of the body, and is thought to reflect the descending inhibition of nociceptive signals.
Methods
The present study examined sex differences in the association between maternal anxiety about pain and children’s CPM responses in 133 healthy children aged 8–17 years. Maternal pain anxiety was assessed using the Pain Anxiety Symptoms Scale-20. In addition to the magnitude of CPM, children’s anticipatory anxiety and pain-related fear of the CPM task were measured.
Results
Sequential multiple linear regression revealed that even after controlling for child age and general maternal psychological distress, greater maternal pain anxiety was significantly related to greater CPM anticipatory anxiety and pain-related fear in girls, and to less CPM (ie, less pain inhibition) in boys.
Conclusion
The findings indicate sex-specific relationships between maternal pain anxiety and children’s responses to a CPM task over and above that accounted for by the age of the child and the mother’s general psychological distress.
doi:10.2147/JPR.S43172
PMCID: PMC3615838  PMID: 23569396
diffuse noxious inhibitory controls; pediatric pain; mother-child relationship; cold pressor; pressure pain; laboratory pain
14.  Experimental pain responses in children with chronic pain and in healthy children: How do they differ? 
BACKGROUND:
Extant research comparing laboratory pain responses of children with chronic pain with healthy controls is mixed, with some studies indicating lower pain responsivity for controls and others showing no differences. Few studies have included different pain modalities or assessment protocols.
OBJECTIVES:
To compare pain responses among 26 children (18 girls) with chronic pain and matched controls (mean age 14.8 years), to laboratory tasks involving thermal heat, pressure and cold pain. Responses to cold pain were assessed using two different protocols: an initial trial of unspecified duration and a second trial of specified duration.
METHODS:
Four trials of pressure pain and of thermal heat pain stimuli, all of unspecified duration, were administered, as well as the two cold pain trials. Heart rate and blood pressure were assessed at baseline and after completion of the pain tasks.
RESULTS:
Pain tolerance and pain intensity did not differ between children with chronic pain and controls for the unspecified trials. For the specified cold pressor trial, 92% of children with chronic pain completed the entire trial compared with only 61.5% of controls. Children with chronic pain exhibited a trend toward higher baseline and postsession heart rate and reported more anxiety and depression symptoms compared with control children.
CONCLUSIONS:
Contextual factors related to the fixed trial may have exerted a greater influence on pain tolerance in children with chronic pain relative to controls. Children with chronic pain demonstrated a tendency toward increased arousal in anticipation of and following pain induction compared with controls.
PMCID: PMC3393051  PMID: 22518373
Acute pain; Cold pressor task; Laboratory pain; Pain intensity; Pressure pain; Thermal heat pain
15.  Sex differences in the relationship between maternal negative life events and children’s laboratory pain responsivity 
Objective
Prior research has demonstrated links between psychosocial factors, including negative life events (NLE) and pain in children. The present study examined sex differences in the relationship between mother-reported NLE, child NLE, mother somatization and children’s laboratory pain responses for heat, cold and pressure pain tasks. We predicted that maternal NLE would be moderately associated with girls’ pain responses, but would not be associated with boys’ pain responses.
Method
Participants were 176 non-clinical children (89 boys) aged 8–18 years (mean = 12.2, SD = 2.7) and their mothers. Mothers and children completed questionnaires assessing their perceptions of NLE experienced in the previous 12 months.
Results
Contrary to predictions, maternal NLE were related to pain responses in both boys and girls, although in opposite directions. Thus, increased maternal stress was associated with increased pain responses in girls but with decreased pain responses in boys. In addition, the impact of maternal NLE was only apparent for heat and pain tasks, indicating differential effects for various types of pain.
Conclusion
The current findings underscore the importance of family variables in understanding sex differences in children’s pain. Future research is needed to examine the mechanisms within the parent-child relationship that contribute to sex-differentiated pain outcomes, particularly under conditions of exacerbated parental stress.
doi:10.1097/DBP.0b013e3181b0ffe4
PMCID: PMC2813770  PMID: 19668092
negative life events; children’s laboratory pain; sex differences
16.  Anxiety Sensitivity and Pain-related Anxiety in the Prediction of Fear Responding to Bodily Sensations: A Laboratory Test 
Journal of psychosomatic research  2010;70(3):258-266.
Objective
The present investigation sought to examine the simultaneous effects of anxiety sensitivity and pain-related anxiety on fear and anxious responding to a 10% carbon dioxide enriched air challenge.
Methods
Participants included 247 adults (53% women; age M = 21.91 years, SD = 8.41) recruited from the community. At the laboratory, participants were administered a structured clinical interview, completed a battery of self-report measures, and underwent a 10% carbon dioxide enriched air challenge.
Results
Both anxiety sensitivity and pain-related anxiety were significantly and uniquely predictive of post-challenge panic attacks, total post-challenge panic attack symptoms, and intensity of cognitive panic attack symptoms. Anxiety sensitivity, but not pain-related anxiety, also was predictive of post-challenge physical panic symptoms. The observed significant effects for both anxiety sensitivity and pain-related anxiety were evident above and beyond the variance accounted for by gender, age, current level of non-specific bodily pain, and negative affectivity. Neither anxiety sensitivity nor pain-related anxiety was significantly predictive of change in anxiety focused on bodily sensations or heart rate.
Conclusion
Results suggest that anxiety sensitivity and pain-related anxiety, although related to one another, may be independently important variables underlying fear reactivity to bodily sensations.
doi:10.1016/j.jpsychores.2010.07.011
PMCID: PMC3052923  PMID: 21334497
Panic; Anxiety; Anxiety Sensitivity; Pain-anxiety; Pain
17.  Alexithymia and fear of pain independently predict heat pain intensity ratings among undergraduate university students 
BACKGROUND:
Alexithymia is a disturbance in awareness and cognitive processing of affect that is associated with over-reporting of physical symptoms, including pain. The relationship between alexithymia and other psychological constructs that are often associated with pain has yet to be evaluated.
OBJECTIVES:
The present study examined the importance of alexithymia in the pain experience in relation to other integral psychological components of Turk’s diathesis-stress model of chronic pain and disability, including fear of pain, anxiety sensitivity, pain avoidance and pain catastrophizing.
METHODS:
Heat pain stimuli, using a magnitude estimation procedure, and five questionnaires (Anxiety Sensitivity Index, Fear of Pain Questionnaire III, Pain Catastrophizing Scale, avoidance subscale of the Pain Anxiety Symptoms Scale-20 and Toronto Alexithymia Scale-20) were administered to 67 undergraduate students (44 women) with a mean (± SD) age of 20.39±3.77 years.
RESULTS:
Multiple linear regression analysis revealed that sex, fear of pain and alexithymia were the only significant predictors of average heat pain intensity (F[6, 60]=5.43; R2=0.35; P=0.008), accounting for 6.8%, 20.0% and 9.6% of unique variance, respectively. Moreover, the difficulty identifying feelings and difficulty describing feelings subscales, but not the externally oriented thinking subscale of the Toronto Alexithymia Scale-20 significantly predicted average heat pain intensity.
CONCLUSIONS:
Individuals with higher levels of alexithymia or increased fear of pain reported higher average pain intensity ratings. The relationship between alexithymia and pain intensity was unrelated to other psychological constructs usually associated with pain. These findings suggest that difficulties with emotion regulation, either through reduced emotional awareness via alexithymia or heightened emotional awareness via fear of pain, may negatively impact the pain experience.
PMCID: PMC2734517  PMID: 19714270
Alexithymia; Fear of pain; Heat pain stimulation; Pain intensity; Undergraduates
18.  Anxiety and functional disability in a large sample of children and adolescents with chronic pain 
BACKGROUND:
Anxiety is the most common psychiatric condition in children and adolescents, and is linked to significant disruptions across domains of function. Due to the avoidant nature of anxiety and pain-related disability, studying anxiety symptoms in children with chronic and recurrent pain conditions is important.
OBJECTIVES:
To examine anxiety symptoms in a large cohort of children and adolescents evaluated for complex chronic and recurrent pain conditions.
METHODS:
Through retrospective chart review, data on anxiety, pain and functional disability were collected from 655 children evaluated at a multidisciplinary pain clinic over a three-year period.
RESULTS:
Approximately 11% of children and adolescents reported clinically elevated anxiety symptoms, with elevated levels across dimensions of anxiety ranging from 14% (social anxiety, worry) to 27% (physiological). In addition, a notable 31% of the sample potentially minimized their anxiety by responding in a socially desirable manner. Anxiety was linearly associated with greater pain-related functional disability, but was not directly correlated with pain. Moderation analyses revealed that at low levels of worry, higher levels of pain were associated with greater functional disability, whereas at high levels of worry, pain no longer predicted the level of functional disability.
CONCLUSIONS:
These findings document the prevalence of anxiety in children and adolescents with chronic pain, and also extend recent studies examining the complex relationships among pain, anxiety and pain-related disability.
PMCID: PMC3393050  PMID: 22518371
Adolescents; Anxiety; Chronic pain; Functional disability; Psychosocial functioning
19.  A Novel Tool for the Assessment of Pain: Validation in Low Back Pain 
PLoS Medicine  2009;6(4):e1000047.
Joachim Scholz and colleagues develop and validate an assessment tool that distinguishes between radicular and axial low back pain.
Background
Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology.
Methods and Findings
Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%–97%) and specificity (97%; 95% CI 89%–100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs.
Conclusions
We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.
Editors' Summary
Background
Pain, although unpleasant, is essential for survival. Whenever the body is damaged, nerve cells detecting the injury send an electrical message via the spinal cord to the brain and, as a result, action is taken to prevent further damage. Usually pain is short-lived, but sometimes it continues for weeks, months, or years. Long-lasting (chronic) pain can be caused by an ongoing, often inflammatory condition (for example, arthritis) or by damage to the nervous system itself—experts call this “neuropathic” pain. Damage to the brain or spinal cord causes central neuropathic pain; damage to the nerves that convey information from distant parts of the body to the spinal cord causes peripheral neuropathic pain. One example of peripheral neuropathic pain is “radicular” low back pain (also called sciatica). This is pain that radiates from the back into the legs. By contrast, axial back pain (the most common type of low back pain) is confined to the lower back and is non-neuropathic.
Why Was This Study Done?
Chronic pain is very common—nearly 10% of American adults have frequent back pain, for example—and there are many treatments for it, including rest, regulated exercise (physical therapy), pain-killing drugs (analgesics), and surgery. However, the best treatment for any individual depends on the exact nature of their pain, so it is important to assess their pain carefully before starting treatment. This is usually done by scoring overall pain intensity, but this assessment does not reflect the characteristics of the pain (for example, whether it occurs spontaneously or in response to external stimuli) or the complex biological processes involved in pain generation. An assessment designed to take such factors into account might improve treatment outcomes and could be useful in the development of new therapies. In this study, the researchers develop and test a new, standardized tool for the assessment of chronic pain that, by examining many symptoms and signs, aims to distinguish between pain subtypes.
What Did the Researchers Do and Find?
One hundred thirty patients with several types of peripheral neuropathic pain and 57 patients with non-neuropathic (axial) low back pain completed a structured interview of 16 questions and a standardized bedside examination of 23 tests. Patients were asked, for example, to choose words that described their pain from a list provided by the researchers and to grade the intensity of particular aspects of their pain from zero (no pain) to ten (the maximum imaginable pain). Bedside tests included measurements of responses to light touch, pinprick, and vibration—chronic pain often alters responses to harmless stimuli. Using “hierarchical cluster analysis,” the researchers identified six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain based on the patterns of symptoms and signs revealed by the interviews and physical tests. They then used “classification tree analysis” to identify the six questions and ten physical tests that discriminated best between pain subtypes and combined these items into a tool for a Standardized Evaluation of Pain (StEP). Finally, the researchers asked whether StEP, which took 10–15 minutes, could identify patients with radicular back pain and discriminate them from those with axial back pain in an independent group of 137 patients with chronic low back pain. StEP, they report, accurately diagnosed these two conditions and was well accepted by the patients.
What Do These Findings Mean?
These findings indicate that a standardized assessment of pain-related signs and symptoms can provide a simple, quick diagnostic procedure that distinguishes between radicular (neuropathic) and axial (non-neuropathic) low back pain. This distinction is crucial because these types of back pain are best treated in different ways. In addition, the findings suggest that it might be possible to identify additional pain subtypes using StEP. Because these subtypes may represent conditions in which different pain mechanisms are acting, classifying patients in this way might eventually enable physicians to tailor treatments for chronic pain to the specific needs of individual patients rather than, as at present, largely guessing which of the available treatments is likely to work best.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000047.
This study is further discussed in a PLoS Medicine Perspective by Giorgio Cruccu and and Andrea Truini
The US National Institute of Neurological Disorders and Stroke provides a primer on pain in English and Spanish
In its 2006 report on the health status of the US, the National Center for Health Statistics provides a special feature on the epidemiology of pain, including back pain
The Pain Treatment Topics Web site is a resource, sponsored partly by associations and manufacturers, that provides information on all aspects of pain and its treatment for health care professionals and their patients
Medline Plus provides a brief description of pain and of back pain and links to further information on both topics (in English and Spanish)
The MedlinePlus Medical Encyclopedia also has a page on low back pain (in English and Spanish)
doi:10.1371/journal.pmed.1000047
PMCID: PMC2661253  PMID: 19360087
20.  Associations between parent and child pain and functioning in a pediatric chronic pain sample: A mixed methods approach 
This study employed a mixed-method design to test sex-specific parent-child pain associations. Subjects were 179 chronic pain patients aged 11–19 years (mean = 14.34; 72% female) presenting for treatment at a multidisciplinary, tertiary clinic. Mothers and children completed questionnaires prior to their clinic visit, including measures of children’s pain, functioning and psychological characteristics. Mothers also reported on their own pain and psychological functioning. Interviews were conducted with a sub-sample of 34 mothers and children prior to the clinic visit and analyzed using a grounded theory approach. The quantitative data suggest stronger mother-daughter than mother-son pain relationships. The qualitative data suggest that girls’ pain and pain-related disability is related to an overly enmeshed mother-daughter relationship and the presence of maternal models of pain, while boys’ pain and disability is linked to male pain models and criticism and to maternal worry and solicitousness. Boys and girls appear to have developmentally incongruous levels of autonomy and conformity to maternal expectations. The mixed-method data suggest distinct trajectories through which mother and father involvement may be linked to chronic pain in adolescent boys and girls.
PMCID: PMC3105525  PMID: 21643522
Sex differences; parent-child relationships; chronic pain
21.  Cognitive processing styles of children and adolescents with headache and back pain: a longitudinal epidemiological study 
Journal of Pain Research  2014;7:405-414.
Background
Previous research has shown positive relationships between dysfunctional cognitive styles and different aspects of pain (eg, pain frequency). One goal of our longitudinal study was to investigate potential risk factors for the incidence of headache (HA) and back pain (BP).
Methods
In the first wave (2003), questionnaires were sent to 6,400 children between the ages of 9 and 14 years. Those who answered in wave 1 were contacted again every year (four survey waves in total: 2003–2006). The data presented are based on the children’s self-reports in the second wave (2004) and third wave (2005). Potential risk factors (dysfunctional stress coping, pain catastrophizing, anxiety sensitivity, and somatosensory amplification) were collected in wave 2. Binary logistic regression analyses – for boys and girls – were performed to assess the predictive value of the risk factors for HA and BP in wave 3.
Results
In the comprehensive model, none of the examined variables predicted the incidence of HA. Anxiety sensitivity increased the risk that boys would report BP after 1 year by 50% and dysfunctional stress coping increased the risk by 40%. For girls, somatosensory amplification increased the risk of the incidence of BP 1 year later by 80%, whereas pain catastrophizing reduced the risk by 50%.
Conclusion
In this incidence sample, the amount of variance explained by the psychological variables investigated was very small. Integrating this result with existing findings from cross-sectional studies suggests that dysfunctional cognitive processing styles may develop more as a consequence or a concomitant feature of BP or HA, but play a less important role in its initial development.
doi:10.2147/JPR.S64334
PMCID: PMC4096452  PMID: 25031545
longitudinal study; risk factors; coping; incidence
22.  The Long-Term Effects of a Peer-Led Sex Education Programme (RIPPLE): A Cluster Randomised Trial in Schools in England 
PLoS Medicine  2008;5(11):e224.
Background
Peer-led sex education is widely believed to be an effective approach to reducing unsafe sex among young people, but reliable evidence from long-term studies is lacking. To assess the effectiveness of one form of school-based peer-led sex education in reducing unintended teenage pregnancy, we did a cluster (school) randomised trial with 7 y of follow-up.
Methods and Findings
Twenty-seven representative schools in England, with over 9,000 pupils aged 13–14 y at baseline, took part in the trial. Schools were randomised to either peer-led sex education (intervention) or to continue their usual teacher-led sex education (control). Peer educators, aged 16–17 y, were trained to deliver three 1-h classroom sessions of sex education to 13- to 14-y-old pupils from the same schools. The sessions used participatory learning methods designed to improve the younger pupils' skills in sexual communication and condom use and their knowledge about pregnancy, sexually transmitted infections (STIs), contraception, and local sexual health services. Main outcome measures were abortion and live births by age 20 y, determined by anonymised linkage of girls to routine (statutory) data. Assessment of these outcomes was blind to sex education allocation. The proportion of girls who had one or more abortions before age 20 y was the same in each arm (intervention, 5.0% [95% confidence interval (CI) 4.0%–6.3%]; control, 5.0% [95% CI 4.0%–6.4%]). The odds ratio (OR) adjusted for randomisation strata was 1.07 (95% CI 0.80–1.42, p = 0.64, intervention versus control). The proportion of girls with one or more live births by 20.5 y was 7.5% (95% CI 5.9%–9.6%) in the intervention arm and 10.6% (95% CI 6.8%–16.1%) in the control arm, adjusted OR 0.77 (0.51–1.15). Fewer girls in the peer-led arm self-reported a pregnancy by age 18 y (7.2% intervention versus 11.2% control, adjusted OR 0.62 [95% CI 0.42–0.91], weighted for non-response; response rate 61% intervention, 45% control). There were no significant differences for girls or boys in self-reported unprotected first sex, regretted or pressured sex, quality of current sexual relationship, diagnosed sexually transmitted diseases, or ability to identify local sexual health services.
Conclusion
Compared with conventional school sex education at age 13–14 y, this form of peer-led sex education was not associated with change in teenage abortions, but may have led to fewer teenage births and was popular with pupils. It merits consideration within broader teenage pregnancy prevention strategies.
Trial registration:
ISRCTN (ISRCTN94255362).
Judith Stephenson and colleagues report on a cluster randomized trial in London of school-based peer-led sex education and whether it reduced unintended teenage pregnancy.
Editors' Summary
Background.
Teenage pregnancies are fraught with problems. Children born to teenage mothers are often underweight, which can affect their long-term health; young mothers have a high risk of poor mental health after the birth; and teenage parents and their children are at increased risk of living in poverty. Little wonder, then, that faced with one of the highest teenage pregnancy rates in Western Europe, the Department of Health in England launched a national Teenage Pregnancy Strategy in 2000 to reduce teenage pregnancies. The main goal of the strategy is to halve the 1998 under-18 pregnancy rate—there were 46.6 pregnancies for every 1,000 young women in this age group in that year—by 2010. Approaches recommended in the strategy to achieve this goal include the provision of effective sexual health advice services for young people, active engagement of health, social, youth support, and other services in the reduction of teenage pregnancies, and the improvement of sex and relationships education (SRE).
Why Was This Study Done?
Although the annual under-18 pregnancy rate in England is falling, it is still very high, and it is extremely unlikely that the main goal of the Teenage Pregnancy Strategy will be achieved. Experts are, therefore, looking for better ways to reduce both teenage pregnancy rates and the high rates of sexual transmitted diseases among teenagers. Many believe that peer-led SRE—the teaching (sharing) of sexual health information, values, and behaviours by people of a similar age or status group—might be a good approach to try. Peers, they suggest, might convey information about sexual health and relationships better than teachers. However, little is known about the long-term effectiveness of peer-led SRE. In this randomized cluster trial, the researchers compare the effects of a peer-led SRE program and teacher-led sex education given to13- to 14-y-old pupils on abortion and live birth numbers among young women up to age 20 y. In a cluster randomized trial, participants are randomly assigned to the interventions being compared in “clusters”; in this trial, each “cluster” is a school.
What Did the Researchers Do and Find?
Twenty-seven schools in England (about 9,000 13- to 14-y-old pupils) participated in the RIPPLE (Randomized Intervention of PuPil-Led sex Education) trial. Each school was randomly assigned to peer-led SRE (the intervention arm) or to existing teacher-led SRE (the control arm). For peer-led SRE, trained 16- to 17-y-old peer educators gave three 1-h SRE sessions to the younger pupils in their schools. These sessions included practice with condoms, role play to improve sexual negotiating skills, and exercises to improve knowledge about sexual health. The researchers then used routine data on abortions and live births to find out how many female study participants had had an unintended pregnancy before the age of 20 y. One in 20 girls in both study arms had had one or more abortions. Slightly more girls in the control arm than in the intervention arm had had live births, but the difference was small and might have occurred by chance. However, significantly more girls in the intervention arm (11.2%) self-reported a pregnancy by age 18 than in the intervention arm (7.2%). There were no differences between the two arms for girls or boys in any other aspect of sexual health, including sexually transmitted diseases.
What Do These Findings Mean?
These findings indicate that the peer-led SRE program used in this trial had no effect on the number of teenage abortions but may have led to slightly fewer live births among the young women in the study. This particular peer-led SRE program was very short so a more extended program might have had a more marked effect on teenage pregnancy rates; this possibility needs to be tested, particularly since the pupils preferred peer-led SRE to teacher-led SRE. Even though peer-led SRE requires more resources than teacher-led SRE, this form of SRE should probably still be considered as part of a broad teenage prevention strategy, suggest the researchers. But, they warn, their findings should also “temper high expectations about the long-term impact of peer-led approaches” on young people's sexual health.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050224.
This study is further discussed in a PLoS Medicine Perspective by David Ross
Every Child Matters, a Web site produced by the UK government, includes information on teenage pregnancy, the Teenage Pregnancy Strategy, and teenage pregnancy statistics in England
Directgov, an official government Web site for UK citizens, provides advice for parents on talking to children about sex and teenage pregnancyand advice for young people on sexual health and preventing pregnancy
Teachernet, a UK source of online publications for schools, also provides information for parents about sex and relationships education and the UK government's current guidance on SRE in schools
Avert, an international AIDS charity, also provides a fact sheet on sex education
The Sex Education Forum in the UK is the national authority on Sex and Relationships Education
doi:10.1371/journal.pmed.0050224
PMCID: PMC2586352  PMID: 19067478
23.  Measuring anxious responses to predictable and unpredictable threat in children and adolescents 
Research has highlighted the need for new methods to assess emotions in children on multiple levels in order to gain better insight into the complex processes of emotional development. The startle reflex is a unique translational tool that has been utilized to study physiological processes during fear and anxiety in rodents and in human subjects. However, it has been challenging to implement developmentally-appropriate startle experiments in children. This paper describes a procedure that uses predictable and unpredictable aversive events to distinguish between phasic fear and sustained anxiety in children and adolescents. We investigated anxious responses, as measured with the startle reflex, in youth (N = 36, mean age[range] = 12.63 [7–17]) across three conditions: no aversive events (N), predictable aversive events (P), and unpredictable aversive events (U). Short-duration cues were presented several times in each condition. Aversive events were signaled by the cues in P, but were presented randomly in U. Participants showed fear-potentiated startle to the threat cue in P. Startle responses were also elevated between cues in U compared to N, suggesting that unpredictable aversive events can evoke a sustained state of anxiety in youth. This latter effect was influenced by sex, being greater in girls compared to boys. These findings indicate the feasibility of this experimental induction of the startle reflex in response to predictable and unpredictable events in children and adolescents, enabling future research on inter-individual differences in fear and anxiety and their development in youth.
doi:10.1016/j.jecp.2011.02.014
PMCID: PMC3110515  PMID: 21440905
fear; anxiety; unpredictability; psychophysiology; startle reflex; sex differences
24.  Breathlessness With Pulmonary Metastases: A Multimodal Approach 
Case Study 
Sarah is a 58-year-old breast cancer survivor, social worker, and health-care administrator at a long-term care facility. She lives with her husband and enjoys gardening and reading. She has two grown children and three grandchildren who live approximately 180 miles away.
SECOND CANCER DIAGNOSIS 
One morning while showering, Sarah detected a painless quarter-sized lump on her inner thigh. While she thought it was unusual, she felt it would probably go away. One month later, she felt the lump again; she thought that it had grown, so she scheduled a visit with her primary care physician. A CT scan revealed a 6.2-cm soft-tissue mass in the left groin. She was referred to an oncologic surgeon and underwent an excision of the groin mass. Pathology revealed a grade 3 malignant melanoma. She was later tested and found to have BRAF-negative status. Following her recovery from surgery, Sarah was further evaluated with an MRI scan of the brain, which was negative, and a PET scan, which revealed two nodules in the left lung.
As Sarah had attended a cancer support group during her breast cancer treatment in the past, she decided to go back to the group when she learned of her melanoma diagnosis. While the treatment options for her lung lesions included interleukin-2, ipilimumab (Yervoy), temozolomide, dacarbazine, a clinical trial, or radiosurgery, Sarah's oncologist felt that ipilimumab or radiosurgery would be the best course of action. She shared with her support group that she was ambivalent about this decision, as she had experienced profound fatigue and nausea with chemotherapy during her past treatment for breast cancer. She eventually opted to undergo stereotactic radiosurgery.
DISEASE RECURRENCE 
After the radiosurgery, Sarah was followed every 2 months. She complained of shortness of breath about 2 weeks prior to each follow-up visit. Each time her chest x-ray was normal, and she eventually believed that her breathlessness was anxiety-related. Unfortunately, Sarah’s 1-year follow-up exam revealed a 2 cm × 3 cm mass in her left lung, for which she had a surgical wedge resection. Her complaints of shortness of breath increased following the surgery and occurred most often with anxiety, heat, and gardening activities, especially when she needed to bend over. Sarah also complained of a burning "pins and needles" sensation at the surgical chest wall site that was bothersome and would wake her up at night.
Sarah met with the nurse practitioner in the symptom management clinic to discuss her concerns. Upon physical examination, observable signs of breathlessness were lacking, and oxygen saturation remained stable at 94%, but Sarah rated her breathlessness as 7 on the 0 to 10 Borg scale. The nurse practitioner prescribed duloxetine to help manage the surgical site neuropathic pain and to assist with anxiety, which in turn could possibly improve Sarah’s breathlessness. Several nonpharmacologic modalities for breathlessness were also recommended: using a fan directed toward her face, working in the garden in the early morning when the weather is cooler, gardening in containers that are at eye level to avoid the need to bend down, and performing relaxation exercises with pursed lip breathing to relieve anxiety-provoked breathlessness. One month later, Sarah reported relief of her anxiety; she stated that the fan directed toward her face helped most when she started to feel "air hungry." She rated her breathlessness at 4/10 on the Borg scale.
SECOND RECURRENCE: MULTIPLE PULMONARY NODULES 
Sarah’s chest x-rays remained clear for 6 months, but she developed a chronic cough shortly before the 9-month exam. An x-ray revealed several bilateral lung lesions and growth in the area of the previously resected lung nodule. Systemic therapy was recommended, and she underwent two cycles of ipilimumab. Sarah’s cough and breathlessness worsened, she developed colitis, and she decided to stop therapy after the third cycle. In addition, her coughing spells triggered bronchospasms that resulted in severe anxiety, panic attacks, and air hunger. She rated her breathlessness at 10/10 on the Borg scale during these episodes. She found communication difficult due to the cough and began to isolate herself. She continued to attend the support group weekly but had difficulty participating in conversation due to her cough.
Sarah was seen in the symptom management clinic every 2 weeks or more often as needed. No acute distress was present at the beginning of each visit, but when Sarah began to talk about her symptoms and fear of dying, her shortness of breath and anxiety increased. The symptom management nurse practitioner treated the suspected underlying cause of the breathlessness and prescribed oral lorazepam (0.5 to 1 mg every 6 hours) for anxiety and codeine cough syrup for the cough. Opioids were initiated for chest wall pain and to control the breathlessness. Controlled-release oxycodone was started at 10 mg every 12 hours with a breakthrough pain (BTP) dose of 5 mg every 2 hours as needed for breathlessness or pain. Sarah noted improvement in her symptoms and reported a Borg scale rating of 5/10. Oxygen therapy was attempted, but subjective improvement in Sarah’s breathlessness was lacking.
END OF LIFE 
Sarah’s disease progressed to the liver, and she began experiencing more notable signs of breathlessness: nasal flaring, tachycardia, and restlessness. Opioid doses were titrated over the course of 3 months to oxycodone (40 mg every 12 hours) with a BTP dose of 10 to 15 mg every 2 hours as needed, but her breathlessness caused significant distress, which she rated 8/10. The oxycodone was rotated to IV morphine continuous infusion with patient-controlled analgesia (PCA) that was delivered through her implantable port. This combination allowed Sarah to depress the PCA as needed and achieve immediate control of her dyspneic episodes. Oral lorazepam was also continued as needed.
Sarah’s daughter moved home to take care of her mother, and hospice became involved for end-of-life care. As Sarah became less responsive, nurses maintained doses of morphine for control of pain and breathlessness and used a respiratory distress observation scale to assess for breathlessness since Sarah could no longer self-report. A bolus PCA dose of morphine was administered by Sarah’s daughter if her mother appeared to be in distress. Sarah died peacefully in her home without signs of distress.
PMCID: PMC4093448  PMID: 25032021
25.  Relationship of child perceptions of maternal pain to children’s laboratory and nonlaboratory pain 
Previous research has established links between parent and child pain. However, little is known about sex-specific parent-child pain relationships in a nonclinical population. A sample of 186 children aged eight to 18 years (49% female) provided information on maternal and self bodily pain, assessed by asking children about the presence and location of bodily pain experienced. Children also completed three laboratory pain tasks and reported on cold pressor pain intensity, pressure pain intensity and heat pain intensity. The presence of child-reported maternal pain was consistently correlated with daughters’ bodily and laboratory pain, but not with sons’ pain in bivariate analyses. Multivariate analyses controlling for child age and maternal psychological distress indicated that children of mothers with bodily pain reported more total bodily pain sites as well as greater pressure and cold pain intensity, relative to children of mothers without bodily pain. For cold pain intensity, these results differed for boys versus girls, in that daughters reporting maternal pain evidenced significantly higher cold pain intensity compared with daughters not reporting maternal pain. No such differences were found for boys. The findings suggest that children’s perceptions of maternal pain may play a role in influencing children’s own experience of pain, and that maternal pain models may affect boys and girls differently.
PMCID: PMC2642517  PMID: 18592057
Children; Pain; Sex differences; Social learning

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