Is pain perception altered in people with depression? A systematic review and meta-analysis of experimental pain research

While clinical studies suggest depressed patients may be more vulnerable to pain, experimental research is equivocal. This meta-analysis aimed to clarify whether depression is associated with altered pain perception in response to noxious stimulation and to identify factors that might influence this association. A search of major electronic databases was conducted to identify experimental studies investigating pain response in depressed participants vs. healthy controls using established pain outcome measures. Random effects meta-analysis of standardized mean differences was conducted on data from 32 studies (N=1,317). For high-intensity noxious stimulation, overall pain tolerance was similar across depressed and control groups (Hedge's g=0.09, p=0.71, studies=10). For low-intensity stimulation, a small, but statistically significant higher mean sensory threshold (g=0.35, p=0.01, studies=9) and pain threshold (g=0.32, p=0.02, studies=25) was observed in depressed participants, suggesting diminished pain. However, considerable heterogeneity in the direction and magnitude of effects was observed, indicating a likely condition-specific impact of depression on pain. Subgroup analysis found that pain threshold/tolerance was increased in depression for exteroceptive (cutaneous) stimulation but decreased for interoceptive (ischemic) stimulation, but that substantial heterogeneity remained. Overall, results provide some support for altered pain processing in depression, but suggest this link is dependent upon modality and additional, unidentified factors

NMDA receptor antagonists and pain relief: A meta-analysis of experimental trials

OBJECTIVES: We conducted a meta-analysis of controlled trials that used experimental models of acute pain and hyperalgesia to examine the analgesic effects of N-methyl-D-aspartate receptor (NMDAR) antagonists. METHODS: Six major databases were systematically searched (to 03/2018) for studies using human evoked pain models to compare NMDAR antagonists with no-intervention controls. Pain outcome data were analyzed with random-effects meta-analysis. RESULTS: Searches identified 70 eligible trials (N=1069). Meta-analysis found that low-dose ketamine (<1 mg/kg) produced a decrease in the size of hyperalgesic area (Standardized Mean Difference=0.54, CI95[0.34, 0.74], p<.001), and a 1.2-point decrease (CI95[0.88, 1.44], p<.001) in pain ratings from 4.6 to 3.4 on a 0-10 scale (a 26% reduction). Similar analgesia was observed for acute and hyperalgesic models and was constant across the dosing range (0.03-1.00 mg/kg). Moderate-high variability in effect size was observed and mild side effects (e.g. sedation, sensory disturbance) were common. No effects of dextromethorphan were found. CONCLUSIONS: Findings provide robust evidence for analgesic and anti-hyperalgesic effects of ketamine, supporting its utility for acute and chronic pain management. However, pain relief was modest, suggesting ketamine may potentially be most useful when opioids are contraindicated, rapid analgesia is required or for pain resistant to conventional medication

Psychosocial and productivity impact of caring for a child with peanut allergy

Background Limited previous research has assessed the psychosocial burden and productivity impact of caring for a child with peanut allergy and factors associated with burden. The objective of this research was to explore caregiver burden in terms of psychosocial and productivity impact of caring for a child with peanut allergy, the influence of caregiver and child gender on caregiver burden, and factors predicting caregiver burden in peanut allergy. Methods A cross-sectional survey of caregivers of children with peanut allergy was conducted in the United Kingdom, and included sociodemographic and clinical questions, EQ-5D, Hospital Anxiety and Depression Scale, Food Allergy Quality of Life-Parental Burden, Food Allergy Independent Measure, and productivity questions. Results One hundred caregivers (55% female) of children with peanut allergy (aged 4–15 years) completed the survey. Male and female caregivers reported mean levels of anxiety significantly higher than United Kingdom population norms. Caregivers of children with severe peanut allergy reported significant impacts on their careers and health-related quality of life. Neither caregiver nor child gender impacted burden, indicating that male and female caregivers are equally anxious and suffer the same level of negative career, productivity, and health-related quality-of-life impact due to their child’s peanut allergy. Caregivers’ perceived risk of outcomes related to their child’s peanut allergy (e.g., death or severe reaction) as measured by the Food Allergy Independent Measure independently predicted burden. Conclusions Caregivers of children with peanut allergy in the United Kingdom experience health-related quality-of-life, psychosocial, and productivity burden; this study demonstrates the high levels of anxiety reported by both male and female caregivers

Social preference weights for treatments in Fabry disease in the UK : a discrete choice experiment

Abstract Objective: Fabry disease is a rare inherited lysosomal storage disorder caused by deficiency of α-galactosidase A. Effective enzyme replacement therapies are available that are administered intravenously. However, a new oral treatment is being developed as an alternative option for patients with amenable mutations. This study was designed to understand the value that people place on the different features of treatments for Fabry disease. Research design and methods: A discrete choice experiment (DCE) was designed to assess the importance of different aspects of treatments for Fabry disease. The attributes included overall survival, mode of administration, treatment related reactions, treatment related headaches and risk of antibody formation. Attributes were combined using a published orthogonal array into choice sets. A research panel was used to survey the UK general public. The mixed logit model was used to estimate strength of preference for the attributes and marginal rates of substitution (MRSs). Disutilities were estimated from the DCE data for changes in each attribute. Results: The sample (n = 506) was broadly representative of UK demographics. The logit model revealed that all attributes were significant predictors of choice. Participants were significantly more likely to choose a treatment which meant an increase in their life expectancy by 1 year (odds ratio = 1.574; 95% CI = 1.504–1.647) and significantly less likely to choose self-administered intravenous (IV) treatment compared to an every other day tablet (OR = 0.426 95% CI = 0.384–0.474). Estimated disutilities were −0.0543 (self-administered infusion), treatment related headaches 12 times a year (−0.0361) and infusion reactions six times a year (−0.0202). Conclusions: The survey revealed a significant preference for oral treatment compared with IV even in the context of a treatment that can extend overall survival. MRSs were used as a basis for estimating disutilities associated with changes in attribute levels which could be used to weight QALYs. It is possible that other important treatment attributes are missing from this research which may have provided further insights. It would also be useful to extend this research to include Fabry disease patients so their preferences can be assessed against the societal perspective

Peanut Allergy impact on PRoductivity and QUAlity of life (PAPRIQUA):Caregiver-reported psychosocial impact of peanut allergy on children

BACKGROUND: Limited research has examined the impact of peanut allergy (PA) on children using validated instruments to assess psychosocial burden and the factors influencing burden. OBJECTIVE: The PAPRIQUA study aimed to assess the caregiver-reported impact of living with PA on children's health-related quality of life (HRQL), correlations between PA severity and child's sex, and associations of caregivers' sex and anxiety with the proxy report of their child's HRQL and to identify significant predictors of a child's HRQL. METHODS: A cross-sectional survey of caregivers of children with mild, moderate and severe PA, based on caregiver perception, was conducted in the United Kingdom. Participants were recruited through a survey recruitment panel; a maximum quota of 20% who rated their child's PA as mild was set to ensure population diversity; however, the quota was not required as few participants considered their child's PA mild. The survey, funded by Aimmune Therapeutics, included sociodemographic and clinical questions, the EQ-5D-Y, Hospital Anxiety and Depression Scale, Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) and Food Allergy Independent Measure (FAIM). RESULTS: One hundred caregivers of children with PA (aged 4-15 years) completed the survey. Child's sex was not associated with proxy-reported burden. For younger children (aged 4-10 years), there was no effect of PA severity; parents of older children (aged 11-15 years) reported low to higher burden for their child on the EQ-5D-Y and FAQLQ-PF dependent upon PA severity. For all measures of child burden except the EQ-5D-Y, two or more reactions in the past 12 months and parental anxiety significantly predicted higher levels of burden for the child (P < .05-P < .001). Experiencing a life-threatening event in the past 12 months significantly predicted EQ-5D-Y proxy utility (P < .01). CONCLUSIONS AND CLINICAL RELEVANCE: Caregivers report that children with PA experience high levels of psychosocial burden, particularly those with more severe PA and a reaction history. Interventions to decrease caregiver anxiety and reaction frequency may help reduce the child's burden. Self-report studies in children with PA would help confirm these findings

Allergy to Peanuts imPacting Emotions And Life (APPEAL): The impact of peanut allergy on children, teenagers, adults and caregivers in the UK and Ireland

The Allergy to Peanuts imPacting Emotions And Life study (APPEAL) explored the psychosocial burden of living with self-reported peanut allergy experienced by children, teenagers, adults and caregivers in the UK and Ireland. A two-stage (quantitative survey and qualitative interview [APPEAL-1]), cross-sectional study of the psychosocial burden of peanut allergy (APPEAL-2) was conducted. Quantitative data were evaluated using descriptive statistics and qualitative data were analysed using MAXQDA software. A conceptual model specific to UK and Ireland was developed using the concepts identified during the analysis. A total of 284 adults in the UK and Ireland completed the APPEAL-1 survey and 42 individuals participated in APPEAL-2. Respondents reported that peanut allergy restricts their choices in various situations, especially with regard to choosing food when eating out (87% moderately or severely restricted), choosing where to eat (82%), special occasions (76%) and when buying food from a shop (71%). Fifty-two percent of survey participants and 40% of interview participants reported being bullied because of PA. Psychological impact of peanut allergy included feeling at least moderate levels of frustration (70%), uncertainty (79%), and stress (71%). The qualitative analysis identified three different types of coping strategies (daily monitoring or vigilance, communication and planning) and four main areas of individuals' lives that are impacted by peanut allergy (social activities, relationships, emotions and work [adults and caregivers only]). The extent of the impact reported varied substantially between participants, with some reporting many negative consequences of living with peanut allergy and others feeling it has minimal impact on their health-related quality of life. This large survey and interview study highlight the psychosocial burden of peanut allergy for adults, teenagers, children and caregivers in the UK and Ireland. The analysis demonstrates the wide variation in level of impact of peanut allergy and the unmet need for those individuals who experience a substantial burden from living with peanut allergy

APPEAL-2: A pan-European qualitative study to explore the burden of peanut-allergic children, teenagers and their caregivers

Background: Allergy to Peanuts ImPacting Emotions And Life (APPEAL-1) was a recent European multi-country questionnaire survey that highlighted the negative impacts of peanut allergy (PA) on quality of life. A follow-on qualitative study, APPEAL-2, further assessed the burden of PA and associated coping strategies through semi-structured interviews. Objective: To gain qualitative insight on the strategies used to cope with and manage PA and the impact of these strategies on the quality of life of children, teenagers and caregivers. Methods: This cross-sectional qualitative study was conducted in eight European countries: the United Kingdom, France, Germany, Ireland, Spain, Italy, Denmark and the Netherlands. Semi-structured interviews were conducted with children (aged 8-12 years) and teenagers (aged 13-17 years) with self-/proxy-reported moderate or severe PA and with parents/caregivers of children or teenagers (aged 4-17 years) with moderate or severe PA. Data were analysed using thematic analysis; data saturation was assessed. Two conceptual models were developed to illustrate the impacts of PA and coping strategies used to manage them for (a) individuals with PA and (b) parents/caregivers of children with PA. Results: 107 participants were interviewed: 24 children, 39 teenagers and 44 caregivers. The conceptual models illustrated themes related to coping and control, driven by the fear of PA reactions, and the associated emotional, social, relationship and work impacts. Factors moderating these impacts included social attitudes and support, child-caregiver relationship and coping strategies used. Conclusions and Clinical Relevance: The APPEAL-2 results substantiate the findings of APPEAL-1; the results also suggest that the severity of experience with PA may not correlate with perception of its overall burden and show variable impacts by country

Pain perception in Parkinson’s disease: A systematic review and meta-analysis of experimental studies

While hyperalgesia (increased pain sensitivity) has been suggested to contribute to the increased prevalence of clinical pain in Parkinson’s disease (PD), experimental research is equivocal and mechanisms are poorly understood. We conducted a meta-analysis of studies comparing PD patients to healthy controls (HCs) in their response to experimental pain stimuli. Articles were acquired through systematic searches of major databases from inception until 10/2016. Twenty-six studies met inclusion criteria, comprising 1292 participants (PD = 739, HCs = 553). Random effects meta-analysis of standardized mean differences (SMD) revealed lower pain threshold (indicating hyperalgesia) in PD patients during unmedicated OFF states (SMD = 0.51) which was attenuated during dopamine-medicated ON states (SMD = 0.23), but unaffected by age, PD duration or PD severity. Analysis of 6 studies employing suprathreshold stimulation paradigms indicated greater pain in PD patients, just failing to reach significance (SMD = 0.30, p= = 0.06). These findings (a) support the existence of hyperalgesia in PD, which could contribute to the onset/intensity of clinical pain, and (b) implicate dopamine deficiency as a potential underlying mechanism, which may present opportunities for the development of novel analgesic strategies

Allergy to Peanuts imPacting Emotions And Life (APPEAL) study : The impact of peanut allergy on children, teenagers, adults and caregivers in Germany

Hintergrund: In Industrieländern sind bis zu 3 % aller Kinder von einer Erdnussallergie betroffen. Allergy to Peanuts imPacting Emotions And Life (APPEAL) ist die erste große Studie, die die Auswirkungen und Belastungen durch eine Erdnussallergie auf Betroffene und Angehörige untersucht. Material und Methoden : Betroffene mit Erdnussallergie und deren Eltern/Betreuer nahmen entweder an einer Online-Umfrage teil (APPEAL‑1, n = 273) oder gaben detaillierte Interviews (APPEAL‑2, n = 32). Ergebnisse : Von den Befragten der APPEAL-1-Studie (56 erwachsene Patienten mit Erdnussallergie und 217 Eltern/Betreuer von Personen mit Erdnussallergie) gaben 85 % an, dass die Erdnussallergie ihre täglichen Aktivitäten beeinflusst, 65 % fühlten sich deshalb isoliert. 91 % sorgten sich besonders bei gesellschaftlichen Anlässen vor einer potenziellen Erdnussexposition; 85 % verspürten Hindernisse beim Pflegen sozialer Kontakte. Die häufigsten psychologischen Auswirkungen der Erdnussallergie waren Frustration (89 %), Unsicherheit (86 %) und Stress (88 %). Ein Großteil der Befragten (84 %) beschrieb ein Gefühl der Andersartigkeit. Durch die Erdnussallergie kommt es häufig zu Beeinträchtigungen bei sozialen Aktivitäten, im schulischen Umfeld, im Beruf (bei Eltern und erwachsenen Betroffenen) sowie in Bezug auf emotionales Befinden und Beziehungen. Als wichtigste Bewältigungsstrategien nannten die Teilnehmer eine gute Überwachung von Nahrung und Hygiene, den Austausch mit anderen und eine akribische Planung von Aktivitäten. Schlussfolgerungen : Dies ist die erste alltagsbezogene Umfrage in Deutschland, die die Auswirkungen und Belastungen einer Erdnussallergie bei betroffenen Kindern, Jugendlichen und deren Eltern/Betreuern sowie bei selbst betroffenen Erwachsenen aufzeigt.Background: Peanut allergy (PA) has been reported to affect up to 3% of children in developed countries. The Allergy to Peanuts imPacting Emotions And Life study (APPEAL) is the first large study to investigate the impact and burden of living with PA in patients and their caregivers. Material and methods: Children, teenagers and adults with PA and their caregivers completed either an online questionnaire (APPEAL‑1, n = 273) or provided in-depth interviews (APPEAL‑2, n = 32). Results: Of the responders in APPEAL‑1 (56 adult patients with PA and 217 parents and caregivers of persons with PA), 85% stated that PA affects their daily activities and 65% felt isolated as a result of living with PA. Feelings of worry about potential exposure to peanuts on social occasions where food is involved were reported by 91% and a total of 85% reported restrictions in socializing. The psychological impact of PA included feelings of frustration (89%), uncertainty (86%) and stress (88%). A large proportion of responders (84%) reported a feeling of differentness due to PA. The main factors that drove the impact of PA included social and school activities, relationships, emotional well-being, and work (parents and caregivers). The main coping strategies to avoid peanuts included monitoring of food and hygiene, communication with others and detailed planning of activities. Conclusion: This is the first real-world survey in Germany to demonstrate the impact and burden of a PA on and unmet needs of allergic children, teenagers and their parents or caregivers as well as affected adults

Appendix 3. Study validity criteria

Appendix 3. Study validity criteri