Publications by authors named "Michael T Smith"

137 Publications

Trait positive affect buffers the association between experimental sleep disruption and inflammation.

Psychoneuroendocrinology 2021 Jul 28;129:105240. Epub 2021 Apr 28.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Sleep disturbances and insufficient sleep are highly prevalent. Both clinical sleep disorders and multiple forms of experimental sleep loss predict heightened inflammation. As such, it is necessary to investigate potential protective factors. Given that trait positive affect (PA) is associated with reduced inflammation, and buffers the proinflammatory effects of stress, it is possible that high trait positive affect might protect individuals from an inflammatory response to sleep disruption. The present study tested this hypothesis in an experimental sleep disruption paradigm with assessment of cellular inflammation.

Methods: Data were drawn from good sleeping adults (n = 79) who participated in a randomized, within-subjects crossover experiment comparing the effects of two nights of sleep disruption versus two nights of uninterrupted sleep. Stimulated monocytic production of intracellular proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) were assayed using flow cytometric methods and indexed as the percentage of monocytes expressing TNF, IL-6, or co-expressing both. Hypotheses were evaluated using linear mixed effects models.

Results: Controlling for negative affect, body mass index, age, and sex, PA significantly moderated the associations between sleep condition and stimulated monocyte production of IL-6 (b = -1.03, t = -2.02, p = .048) and its co-expression with TNF (b = -0.93, t = -2.00, p = .049), such that inflammatory responses were blunted among those high in PA with increases principally among those low in PA. The effect on TNF was similar in terms of effect size, but marginally significant.

Conclusions: Activation of cellular inflammation in response to sleep disruption is buffered by PA independent of negative affect. Interventions that promote PA might protect persons from the inflammatory activation following sleep loss, with the potential to mitigate the adverse health consequences of sleep disturbance.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105240DOI Listing
July 2021

Sex Differences, Sleep Disturbance and Risk of Persistent Pain Associated With Groin Hernia Surgery: A Nationwide Register-Based Cohort Study.

J Pain 2021 May 5. Epub 2021 May 5.

Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Surgery, Skåne University Hospital, Malmö, Sweden.

Persistent pain after groin hernia repair is a major health problem. Sleep disturbance is associated with heightened pain sensitivity. The main objective of this study was to examine the role of sleep disturbance in the development and long-term maintenance of chronic postherniorrhaphy inguinal pain (CPIP), with exploration of sex differences. From 2012 to 2017, a national cohort of patients with prior groin hernia repair (n = 2084;45.8% females) were assessed for the development of CPIP 12 months after surgery. Patients then underwent long-term (median 5.0 years) follow-up to evaluate the contribution of sex and sleep disturbance on the maintenance of CPIP. Associations between pre- and postoperative sleep problems (assessed at long-term follow-up) and CPIP were tested using logistic regression. Females had higher rates of CPIP with negative impact on daily activities 12 months after surgery as compared to males (14.6 vs 9.2%, P < .0005), and were more likely to have moderate-severe CPIP in the long-term (3.1 vs 1.2%, P = .003). Preoperative sleep problems predicted development of CPIP 12 months after surgery (adjusted odds ratio [aOR] 1.76 [95%CI 1.26-2.46], P = .001) and CPIP in the long-term (aOR 2.20 [1.61-3.00] , P < .0001). CPIP was associated with insomnia and depression. Sleep disturbance may increase the risk for CPIP, and contribute to maintenance of postsurgical pain. PERSPECTIVE: Females are at heightened risk for CPIP as compared to males. Increased severity of pain symptoms are linked to poorer sleep and psychiatric morbidity. Given the robust associations between sleep disturbance and CPIP, interventions which consolidate and promote sleep, especially in females, may improve long-term pain control.
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http://dx.doi.org/10.1016/j.jpain.2021.04.008DOI Listing
May 2021

Preoperative sleep quality and adverse pain outcomes after total hip arthroplasty.

Eur J Pain 2021 Mar 8. Epub 2021 Mar 8.

Clinical Memory Research Unit, Faculty of Medicine, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.

Background: Sleep disturbance is thought to aggravate acute postoperative pain. The influence of preoperative sleep problems on pain control in the long-term and development of chronic postsurgical pain is largely unknown.

Methods: This prospective, observational study aimed to examine the links between preoperative sleep disturbance (Pittsburgh Sleep Quality Index, PSQI) and pain severity (Brief Pain Inventory, BPI) 6 months postoperative (primary outcome), objective measures of pain and postoperative pain control variables (secondary outcomes). Patients (n = 52) with disabling osteoarthritis (OA) pain undergoing total hip arthroplasty (THA) were included. Quantitative sensory testing (QST) was performed preoperatively on the day of surgery to evaluate pain objectively. Clinical data, as well as measures of sleep quality and pain, were obtained preoperatively and longitudinally over a 6-month period.

Results: Preoperatively, sleep disturbance (i.e., PSQI score >5) occurred in 73.1% (n = 38) of THA patients, and pain severity was high (BPI pain severity 5.4 ± 1.3). Regression models, adjusting for relevant covariates, showed that preoperative PSQI score predicted pain severity 6 months postoperative (β = 0.091 (95% CI 0.001-0.181), p = .048, R  = 0.35). Poor sleep quality was associated with increased pressure pain sensitivity and impaired endogenous pain inhibitory capacity (R range 0.14-0.33, all p's < 0.04). Moreover, preoperative sleep disturbance predicted increased opioid treatment during the first 24 hr after surgery (unadjusted β = 0.009 (95% CI 0.002-0.015) mg/kg, p = .007, R  = 0.15).

Conclusions: Preoperative sleep disturbance is prevalent in THA patients, is associated with objective measures of pain severity, and independently predicts immediate postoperative opioid treatment and poorer long-term pain control in patients who have undergone THA.

Significance: Poor sleep quality and impaired sleep continuity are associated with heightened pain sensitivity, but previous work has not evaluated whether preoperative sleep problems impact long-term postoperative pain outcomes. Here, we show that sleep difficulties prior to total hip arthroplasty adversely predict postoperative pain control 6 months after surgery. Given sleep difficulties robustly predict pain outcomes, targeting and improving sleep may have salutary effects on postoperative pain reports and management.
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http://dx.doi.org/10.1002/ejp.1761DOI Listing
March 2021

Temporal association of pain catastrophizing and pain severity across the perioperative period: a cross-lagged panel analyses following total knee arthroplasty.

Pain Med 2021 Feb 3. Epub 2021 Feb 3.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.

Objective: While numerous studies show that preoperative pain catastrophizing is a risk factor for pain following total knee arthroplasty (TKA), little is known regarding the temporal course of the association between perioperative pain catastrophizing and pain severity. The present study investigated temporal changes and their dynamic associations between pain catastrophizing and pain severity before and after TKA.

Design: A secondary data analysis of a larger observational parent study featuring prospective repeated measurement over 12 months.

Setting: Dual-site academic hospital.

Subjects: 245 individuals who underwent TKA.

Methods: Participants completed pain catastrophizing and pain severity questionnaires at baseline, 6-weeks, and 3-, 6-, and 12-months post-TKA. Cross-lagged panel analysis was conducted using structural equation modeling including age, sex, race, baseline anxiety and depressive symptoms as covariates.

Results: Reduction in pain catastrophizing from baseline to 6-week post-TKA was associated with lower pain severity at 3-month post-TKA (standardized β = .14; SE = .07, p = .046), while reduction in pain severity at 6-week post-TKA was not associated with pain catastrophizing at 3-month post-TKA (p = .905). In the chronic post-surgical period (>3 months), pain catastrophizing at 6-month post-TKA predicted pain severity at 12 months post-TKA (β = .23, p = .009)] while controlling for auto-correlation and covariates, but not vice versa.

Conclusions: We provide evidence that changes in pain catastrophizing from baseline to 6-week post-TKA are associated with subsequent pain severity. Future studies are warranted to determine whether targeting pain catastrophizing during the perioperative period may improve clinical outcomes for individuals undergoing TKA.
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http://dx.doi.org/10.1093/pm/pnab035DOI Listing
February 2021

Experimental sleep disruption attenuates morphine analgesia: findings from a randomized trial and implications for the opioid abuse epidemic.

Sci Rep 2020 11 18;10(1):20121. Epub 2020 Nov 18.

Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, 90024, USA.

Preclinical studies demonstrate that sleep disruption diminishes morphine analgesia and modulates reward processing. We sought to translate these preclinical findings to humans by examining whether sleep disruption alters morphine's analgesic and hedonic properties. We randomized 100 healthy adults to receive morphine versus placebo after two nights of undisturbed sleep (US) and two nights of forced awakening (FA) sleep disruption. Sleep conditions were counterbalanced, separated by a two-week washout. The morning after both sleep conditions, we tested cold pressor pain tolerance before and 40-min after double-blind injection of .08 mg/kg morphine or placebo. The primary outcome was the analgesia index, calculated as the change in cold pressor hand withdrawal latency (HWL) before and after drug injection. Secondary outcomes were ratings of feeling "high," drug "liking," and negative drug effects. We found a significant sleep condition by drug interaction on the analgesia index (95% CI - 0.57, - 0.001). After US, subjects receiving morphine demonstrated significantly longer HWL compared to placebo (95% CI 0.23, 0.65), but not after FA (95% CI - 0.05, 0.38). Morphine analgesia was diminished threefold under FA, relative to US. After FA, females (95% CI - 0.88, - 0.05), but not males (95% CI - 0.23, 0.72), reported decreased subjective "high" effects compared to US. After FA, females (95% CI 0.05, 0.27), but not males (95% CI - 0.10, 0.11), administered morphine reported increased negative drug effects compared to US. These data demonstrate that sleep disruption attenuates morphine analgesia in humans and suggest that sleep disturbed males may be at greatest risk for problematic opioid use.
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http://dx.doi.org/10.1038/s41598-020-76934-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674501PMC
November 2020

A Preliminary Investigation of the Underlying Mechanism Associating Daily Sleep Continuity Disturbance and Prescription Opioid Use Among Individuals With Sickle Cell Disease.

Ann Behav Med 2021 Jun;55(6):580-591

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Background: There are emerging data indicating that sleep disturbance may be linked with an increase in opioid use. The majority of sickle cell disease (SCD) patients experience sleep disturbances, which can elevate pain severity and pain catastrophizing, both of which are important predictors of opioid consumption.

Purpose: We conducted a preliminary investigation on the association between previous night sleep disturbance and short-acting opioid use, as well as the potential mediating roles of pain severity and pain catastrophizing. Because sex is associated with sleep disturbance, pain-related experiences, and opioid use, we also explored the potential moderating role of sex.

Methods: Participants were 45 SCD patients who were prescribed opioids. For 3 months, sleep diaries were collected immediately upon participants' awakening. Daily pain severity, pain catastrophizing, and prescription opioid use measures were collected before bedtime.

Results: Multilevel structural equation modeling revealed that wake time after sleep onset (WASO) during the previous night (Time 1) predicted greater short-acting opioid use during the next day (Time 2). Pain severity and pain catastrophizing measured during the next day (Time 2) also mediated the association between the two. Sex moderation analysis showed that the positive association between WASO and pain severity was largely driven by women.

Conclusion: These findings provide some preliminary evidence as to the mechanism linking sleep continuity disturbance and opioid requirement in SCD patients. Future studies should replicate and extend these findings with clearer temporal information and employing more refined measures of sleep continuity and prescription opioid use in a larger sample.
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http://dx.doi.org/10.1093/abm/kaaa099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171806PMC
June 2021

Hospitalization and mortality following non-attendance for hemodialysis according to dialysis day of the week: a European cohort study.

BMC Nephrol 2020 06 9;21(1):218. Epub 2020 Jun 9.

Department of Renal Medicine, University College London, London, UK.

Background: The extension of the interdialytic interval due to due to dialysis session non-attendance varies according to which session of the week the patient misses. The impact of this on subsequent hospitalization and mortality is unknown.

Methods: The ARO cohort study prospectively collected data from hemodialysis patients across 15 European countries on demography, comorbidity, laboratory, hospitalisation, mortality and individual hemodialysis sessions from 2007 to 2014. Event rates for death and hospitalisation according to dialysis day of the week were calculated for patients who attended the three previous scheduled hemodialysis sessions, who then on the next scheduled dialysis day either attended or did not attend. The hazard ratio for these events following non-attendance for the first compared to the second dialysis session of the week was estimated using Cox proportional hazards model adjusted for patient demographics.

Results: 3.8 million hemodialysis sessions in 9397 patients were analysed. The non-attendance rates for Monday/Wednesday/Friday sessions were 0.8, 0.9% & 1.4% respectively, and for Tuesday/Thursday/Saturday sessions were 0.6, 1.0% & 1.2% respectively. Compared to those who attended, for the 48-72 h between non-attendance and the next scheduled haemodialysis session, mortality significantly increased from 4.86 to 51.9/100 pt-yrs and hospitalisation increased from 0.58 to 2.1/yr. As time from the two-day break increased, the risk associated with non-attendance lessened: compared to missing the second hemodialysis session, missing the first session had a hazard ratio for mortality of 2.04 (95% CI 1.27-3.29), and for hospitalisation 1.78 (95% CI 1.29-2.47). In patients who attended their scheduled dialysis session and the three preceding, after the two-day break there were absolute increases in mortality (8.3 vs. 4.9/100 pt-yrs) and hospitalisation (1.0 vs. 0.6/yr for the rest of the week) comparable to previous studies.

Conclusions: In addition to hospitalisation and mortality increases seen after the two-day break, additional harm may be manifested in the greater increases in mortality and hospitalisation observed after non-attendance for the first hemodialysis session after the two-day break compared to missing other sessions.
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http://dx.doi.org/10.1186/s12882-020-01874-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285433PMC
June 2020

Sleep disturbance and insomnia in individuals seeking bariatric surgery.

Surg Obes Relat Dis 2020 Jul 18;16(7):940-947. Epub 2020 Mar 18.

Department of Psychiatry & Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland.

Background: Sleep disturbance is well established in individuals with obesity, and the relationship between poor sleep and obesity is supported by population, longitudinal, experimental, and intervention studies. However, the prevalence and characteristics of poor sleep in individuals seeking bariatric surgery have thus far been poorly examined.

Objectives: We sought to characterize self-reported sleep parameters in individuals seeking bariatric surgery and to compare these data with controls.

Setting: Two Academic Medical Centers, United States, and an online survey of healthy controls.

Method: Individuals seeking bariatric surgery (n = 427) completed presurgical psychological evaluations at 2 comprehensive bariatric surgery programs. Data on medical co-morbidities and from self-report questionnaires on sleep quality, insomnia, anxiety, and depression were abstracted from charts. Data from controls (n = 180) were collected using an online survey tool and compared with bariatric cases.

Results: Across study sites, 40.4% of bariatric cases took at least 30 minutes to fall asleep, 46.7% had insufficient total sleep time (<6.5 hr), 65.1% reported general poor sleep quality, and 30.8% reported clinically significant insomnia symptoms. Approximately 20% of the variance in poor sleep quality and insomnia was explained by body mass index, obstructive sleep apnea, anxiety, and depression. Cases and controls were similar, although bariatric cases reported significantly poorer sleep efficiency.

Conclusions: Our results suggest that similar to a control population, the majority of patients seeking bariatric surgery are experiencing sleep difficulties. Presurgical assessment and treatment of sleep problems may be beneficial to patients and may help improve weight loss treatment outcomes. Optimally, assessment would include 1 of the 2 self-report questionnaires used herein, and treatment would involve Cognitive Behavioral Therapy for Insomnia. Future research assessing sleep patterns with objective measurement tools and evaluating the impact of sleep on postsurgical outcomes is warranted.
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http://dx.doi.org/10.1016/j.soard.2020.03.007DOI Listing
July 2020

Multimodal assessment of sleep in men and women during treatment for opioid use disorder.

Drug Alcohol Depend 2020 02 18;207:107698. Epub 2019 Nov 18.

Intramural Research Program, National Institute on Drug Abuse, 251 Bayview Blvd., Suite 200, Baltimore, MD, 21224, United States. Electronic address:

Background: Sleep disturbance is common in patients with opioid use disorder (OUD) receiving medication for addiction treatment. Differences between patients on the two primary agonist medications-methadone and buprenorphine-are not well understood.

Methods: In patients receiving either methadone or buprenorphine treatment for OUD, we examined sleep continuity and architecture using ambulatory monitoring to gather both an objective measure (daily sleep EEG; M = 5.76 days, SD = 1.46) and a subjective measure (daily sleep diary; M = 54.10 days, SD = 25.10) of sleep.

Results: Patients treated with buprenorphine versus methadone did not differ on any measure of sleep continuity or architecture. Women had longer EEG-derived total sleep time than men (d = -0.68, 95 % CI -1.32 to -0.09), along with lower %N2 (d = 0.94, 95 % CI 0.34-1.64) and greater %N3 (d = -0.94, 95 % CI -1.61 to -0.32). Self-reported sleep differed from EEG-derived estimates: wake after sleep onset was greater by EEG than by diary (d = 2.58, 95 % CI 1.74-3.63), and total sleep time and sleep efficiency were lower by EEG than by diary (d for sleep time = 2.93, 95 % CI 2.06-4.14; d for efficiency = 1.69, 95 % CI 0.98-2.49).

Conclusions: Patients treated with buprenorphine or methadone did not substantively differ in ambulatory measures of sleep. With both medications, there was a discrepancy between objective and subjective sleep measures. Further confirmatory evidence would inform the development of sleep-related recommendations for OUD patients undergoing agonist treatment.
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http://dx.doi.org/10.1016/j.drugalcdep.2019.107698DOI Listing
February 2020

Sex Differences in Interleukin-6 Responses Over Time Following Laboratory Pain Testing Among Patients With Knee Osteoarthritis.

J Pain 2020 May - Jun;21(5-6):731-741. Epub 2019 Nov 13.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, Maryland.

Epidemiological studies suggest that women are not only at a higher risk for developing knee osteoarthritis (KOA), but also report greater symptom severity compared to men. One potential underlying mechanism of these sex differences may be exaggerated inflammatory responses to pain among women compared to men. The present study examined sex differences in interleukin-6 (IL-6) response over time following experimental pain testing. We hypothesized that women, when compared to men, would show greater IL-6 reactivity when exposed to acute pain in a human laboratory setting. Eighty-four participants (36 men and 48 women) with KOA scheduled for total knee arthroplasty underwent a quantitative sensory testing (QST) battery. A total of seven IL-6 measurements were taken, twice at baseline, once immediately after QST, and every 30 minutes up to 2 hours after QST. Consistent with our hypothesis, women, when compared to men, showed accelerated increases in IL-6 levels following laboratory-evoked pain, even after controlling for body mass index, marital status, clinical pain, evoked pain sensitivity, and situational pain catastrophizing. Given that KOA is a chronic condition, and individuals with KOA frequently experience pain, these sex differences in IL-6 reactivity may contribute to the maintenance and/or exacerbation of KOA symptoms. PERSPECTIVES: The present study demonstrates that women, when compared to men, exhibit greater IL-6 reactivity after exposure to laboratory-evoked pain. Such sex differences may explain the mechanisms underlying women's higher chronic pain risk and pain perception, as well as provide further insight in developing personalized pain interventions.
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http://dx.doi.org/10.1016/j.jpain.2019.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217718PMC
November 2019

Individual differences in pain sensitivity are associated with cognitive network functional connectivity following one night of experimental sleep disruption.

Hum Brain Mapp 2020 02 16;41(3):581-593. Epub 2019 Oct 16.

Department of Neural and Pain Sciences, School of Dentistry, and Center to Advance Chronic Pain Research, University of Maryland Baltimore, Baltimore, Maryland.

Previous work suggests that sleep disruption can contribute to poor pain modulation. Here, we used experimental sleep disruption to examine the relationship between sleep disruption-induced pain sensitivity and functional connectivity (FC) of cognitive networks contributing to pain modulation. Nineteen healthy individuals underwent two counterbalanced experimental sleep conditions for one night each: uninterrupted sleep versus sleep disruption. Following each condition, participants completed functional MRI including a simple motor task and a noxious thermal stimulation task. Pain ratings and stimulus temperatures from the latter task were combined to calculate a pain sensitivity change score following sleep disruption. This change score was used as a predictor of simple motor task FC changes using bilateral executive control networks (RECN, LECN) and the default mode network (DMN) masks as seed regions of interest (ROIs). Increased pain sensitivity after sleep disruption was positively associated with increased RECN FC to ROIs within the DMN and LECN (F = 25.28, pFDR = 0.05). However, this pain sensitivity change score did not predict FC changes using LECN and DMN masks as seeds (pFDR > 0.05). Given that only RECN FC was associated with sleep loss-induced hyperalgesia, findings suggest that cognitive networks only partially contribute to the sleep-pain dyad.
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http://dx.doi.org/10.1002/hbm.24824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981017PMC
February 2020

Sex differences in negative affect and postoperative pain in patients undergoing total knee arthroplasty.

Biol Sex Differ 2019 05 6;10(1):23. Epub 2019 May 6.

Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA, 02115, USA.

Background: Knee osteoarthritis (OA) is among the most common and disabling persistent pain conditions, with increasing prevalence in the developed world, and affects women to a greater degree than men. In the USA, the growth of knee OA has been paralleled by an increase in rates of total knee arthroplasty (TKA), a surgical treatment option for late-stage knee OA. While TKA outcomes are generally good, postoperative trajectories of pain vary widely, with some patients reporting a complete absence of pain, but with a significant minority reporting worsening pain. Biopsychosocial factors, including anxiety and depression, are known to contribute importantly to the experience of joint pain, with women reporting a higher degree of negative affective symptoms.

Methods: This study investigated sex differences in TKA outcomes in age-matched groups of men and women at two academic medical centers. Pain and physical function were assessed in 100 patients (50 men and 50 women) during the perioperative period (preoperative visit-6 weeks postsurgical). The association of preoperative negative affect (anxiety and depression scores) to postoperative pain and function was evaluated, with specific attention to sex differences in this relationship.

Results: Overall, women reported more baseline pain-related physical dysfunction (although not higher baseline pain scores), as well as higher acute postoperative pain scores during the 2 weeks following TKA than their male counterparts. By 6 weeks postoperatively, sex differences in reported pain were no longer evident. Interestingly, although women reported higher preoperative levels of emotional distress than men, preoperative anxiety and depression scores were better predictors of severe postoperative pain among men than women, throughout the postoperative test period.

Conclusions: This study underlines the importance of considering sex and psychosocial factors, as well as their interaction, in understanding postsurgical pain trajectories.
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http://dx.doi.org/10.1186/s13293-019-0237-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501305PMC
May 2019

Experimental sleep disruption and reward learning: moderating role of positive affect responses.

Sleep 2019 05;42(5)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.

Study Objectives: Sleep disturbances increase vulnerability for depression, but the mechanisms underlying this relationship are not well known. We investigated the effects of experimental sleep disruption on response bias (RB), a measure of reward learning previously linked to depression, and the moderating role of positive affect responses.

Methods: Participants (N = 42) were healthy adults enrolled in a within-subject crossover sleep disruption experiment that incorporated one night of uninterrupted sleep (US) and one night of forced awakenings (FA) in random order. On the day following each experimental sleep night, participants completed a probabilistic reward task to assess RB, and the Positive and Negative Affect Schedule-X. Participants were subgrouped according to positive affect responses: Preserved Positive Affect (i.e. positive affect scores maintained or increased; n = 15) or Reduced Positive Affect (i.e. positive affect scores decreased; n = 27) following FA.

Results: Contrary to our hypotheses, across participants, RB did not significantly differ between the US and FA sleep conditions (p = .67). However, the effect of sleep condition on RB was moderated by positive affect response (p = .01); those with preserved positive affect showed heightened RB following FA, whereas those with reduced positive affect showed diminished RB following FA. Changes in negative affect between US and FA did not moderate RB.

Conclusion: The inability to preserve positive affect through periods of sleep disruption may be a marker of diminished reward learning capability. Understanding how sleep disruption impacts positive affect responses and reward learning identifies a pathway by which sleep disturbances may confer risk for depression.
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http://dx.doi.org/10.1093/sleep/zsz026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519913PMC
May 2019

Complex Patterns of GABAergic Neuronal Deficiency and Type 2 Potassium-Chloride Cotransporter Immaturity in Human Focal Cortical Dysplasia.

J Neuropathol Exp Neurol 2019 04;78(4):365-372

Department of Pathology and Laboratory Medicine.

Focal cortical dysplasia (FCD) is a common histopathologic finding in cortical specimens resected for refractory epilepsy. GABAergic neuronal abnormalities and K-Cl cotransporter type 2 (KCC2) immaturity may be contributing factors for FCD-related epilepsy. We examined surgical specimens from 12 cases diagnosed with FCD, and brain tissues without developmental abnormality obtained from 6 autopsy cases. We found that GABAergic neuronal density was abnormal in FCD with 2 distinct patterns. In 7 of 12 (58%) FCD subjects, the GABAergic neuron density in dysplastic regions and in neighboring nondysplastic regions was equally reduced, hence we call this a "broad pattern." In the remaining cases, GABAergic neuron density was decreased in dysplastic regions but not in the neighboring nondysplastic regions; we designate this "restricted pattern." The different patterns are not associated with pathologic subtypes of FCD. Intracytoplasmic retention of KCC2 is evident in dysmorphic neurons in the majority of FCD type II subjects (5/7) but not in FCD type I. Our study suggests that (1) "broad" GABAergic deficiency may reflect epileptic vulnerability outside the dysplastic area; and (2) abnormal distribution of KCC2 may contribute to seizure generation in patients with FCD type II but not in type I.
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http://dx.doi.org/10.1093/jnen/nlz009DOI Listing
April 2019

Chondrosarcoma Arising in the Mastoid Involving the Intratemporal Facial Nerve.

JAMA Otolaryngol Head Neck Surg 2019 Apr;145(4):392-393

Department of Otolaryngology, Medical University of South Carolina, Charleston.

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http://dx.doi.org/10.1001/jamaoto.2018.4149DOI Listing
April 2019

Pain-related nucleus accumbens function: modulation by reward and sleep disruption.

Pain 2019 05;160(5):1196-1207

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

The nucleus accumbens (NAc) has been implicated in sleep, reward, and pain modulation, but the relationship between these functional roles is unclear. This study aimed to determine whether NAc function at the onset and offset of a noxious thermal stimulus is enhanced by rewarding music, and whether that effect is reversed by experimental sleep disruption. Twenty-one healthy subjects underwent functional magnetic resonance imaging scans on 2 separate days after both uninterrupted sleep and experimental sleep disruption. During functional magnetic resonance imaging scans, participants experienced noxious stimulation while listening to individualized rewarding or neutral music. Behavioral results revealed that rewarding music significantly reduced pain intensity compared with neutral music, and disrupted sleep was associated with decreased pain intensity in the context of listening to music. In whole-brain family-wise error cluster-corrected analysis, the NAc was activated at pain onset, but not during tonic pain or at pain offset. Sleep disruption attenuated NAc activation at pain onset and during tonic pain. Rewarding music altered NAc connectivity with key nodes of the corticostriatal circuits during pain onset. Sleep disruption increased reward-related connectivity between the NAc and the anterior midcingulate cortex at pain onset. This study thus indicates that experimental sleep disruption modulates NAc function during the onset of pain in a manner that may be conditional on the presence of competing reward-related stimuli. These findings point to potential mechanisms for the interaction between sleep, reward, and pain, and suggest that sleep disruption affects both the detection and processing of aversive stimuli that may have important implications for chronic pain.
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http://dx.doi.org/10.1097/j.pain.0000000000001498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213641PMC
May 2019

Analgesic Effects of Hydromorphone versus Buprenorphine in Buprenorphine-maintained Individuals.

Anesthesiology 2019 01;130(1):131-141

From The Johns Hopkins School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, Maryland (A.S.H., E.C.S., G.E.B., M.T.S.) Harvard Medical School, Brigham and Women's Hospital, Department of Anesthesiology, Perioperative, and Pain Medicine, Boston, Massachusetts (R.R.E.) University of California, San Francisco Department of Psychiatry, San Francisco, California (D.A.T.).

Background: Managing acute pain in buprenorphine-maintained individuals in emergency or perioperative settings is a significant challenge. This study compared analgesic and abuse liability effects of adjunct hydromorphone and buprenorphine using quantitative sensory testing, a model of acute clinical pain, in persons maintained on 12 to 16 mg sublingual buprenorphine/naloxone.

Methods: Participants (N = 13) were enrolled in a randomized within-subject, double-blind, placebo-controlled three-session experiment. Each session used a cumulative dosing design with four IV injections (4, 4, 8, and 16 mg of hydromorphone or 4, 4, 8, and 16 mg of buprenorphine); quantitative sensory testing and abuse liability assessments were measured at baseline and after each injection. The primary analgesia outcome was change from baseline cold pressor testing; secondary outcomes included thermal and pressure pain testing, as well as subjective drug effects and adverse events.

Results: A significant two-way interaction between study drug condition and dose was exhibited in cold pressor threshold (F10,110 = 2.14, P = 0.027) and tolerance (F10,110 = 2.69, P = 0.006). Compared to after placebo, participants displayed increased cold pressor threshold from baseline after cumulative doses of 32 mg of IV hydromorphone (means ± SD) (10 ± 14 s, P = 0.035) and 32 mg of buprenorphine (3 ± 5 s, P = 0.0.39) and in cold pressor tolerance after cumulative doses of 16 mg (18 ± 24 s, P = 0.018) and 32 mg (48 ± 73 s, P = 0.041) IV hydromorphone; cold pressor tolerance scores were not significant for 16 mg (1 ± 15 s, P = 0.619) or 32 mg (7 ± 16 s, P = 0.066) buprenorphine. Hydromorphone and buprenorphine compared with placebo showed greater ratings on subjective measures of high, any drug effects, good effects, and drug liking. Adverse events were more frequent during the hydromorphone compared with buprenorphine and placebo conditions for nausea, pruritus, sedation, and vomiting.

Conclusions: In this acute clinical pain model, high doses of IV hydromorphone (16 to 32 mg) were most effective in achieving analgesia but also displayed higher abuse liability and more frequent adverse events. Cold pressor testing was the most consistent measure of opioid-related analgesia.
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http://dx.doi.org/10.1097/ALN.0000000000002492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295244PMC
January 2019

Sex differences in measures of central sensitization and pain sensitivity to experimental sleep disruption: implications for sex differences in chronic pain.

Sleep 2019 02;42(2)

Department of Psychiatry and Behavioral Sciences, Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA.

Study Objectives: Females demonstrate heightened central sensitization (CS), a risk factor for chronic pain characterized by enhanced responsivity of central nervous system nociceptors to normal or subthreshold input. Sleep disruption increases pain sensitivity, but sex has rarely been evaluated as a moderator and few experiments have measured CS. We evaluated whether two nights of sleep disruption alter CS measures of secondary hyperalgesia and mechanical temporal summation in a sex-dependent manner. We also evaluated differences in measures of pain sensitivity.

Methods: Seventy-nine healthy adults (female n = 46) participated in a randomized crossover experiment comparing two consecutive nights of eight pseudorandomly distributed forced awakenings (FA [-200 min sleep time]) against two nights of undisturbed sleep (US). We conducted sensory testing the mornings following Night 2; the heat-capsaicin pain model was used to induce secondary hyperalgesia.

Results: FA reduced total sleep time (REM and NREM Stage 3) more profoundly in males. We observed divergent, sex-dependent effects of FA on secondary hyperalgesia and temporal summation. FA significantly increased secondary hyperalgesia in males and significantly increased temporal summation in females. Sex differences were not attributable to differential sleep loss in males. FA also significantly reduced heat-pain threshold and cold pressor pain tolerance, independently of sex.

Conclusions: Sleep disruption enhances different pain facilitatory measures of CS in males and females suggesting that sleep disturbance may increase risk for chronic pain in males and females via distinct pathways. Findings have implications for understanding sex differences in chronic pain and investigating sleep in chronic pain prevention efforts.
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http://dx.doi.org/10.1093/sleep/zsy209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369729PMC
February 2019

Subjective and Objective Measures of Daytime Activity and Sleep Disturbance in Retinitis Pigmentosa.

Optom Vis Sci 2018 09;95(9):837-843

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland.

Significance: Objectively measured limitations in daytime activity levels appear to be inextricably linked with sleep disturbances in retinitis pigmentosa (RP) patients, as well as associated with unemployment status and central vision loss. Innovative interventional strategies should be developed to help improve these issues and overall quality of life for RP patients.

Purpose: Novel sensor devices are emerging as valuable tools to objectively assess behavior. We used validated measures of wrist accelerometry to determine relationships between sleep, vision, and physical activity in RP subjects.

Methods: For one week, 33 RP adults wore a wrist Actiwatch to detect movement during the day (average total activity counts) and disturbed sleep at night. They completed Early Treatment Diabetic Retinopathy Study visual acuity testing, Pelli-Robson contrast sensitivity, Goldmann V4e visual fields, and sleep diaries and validated questionnaires to assess their sleep and general health.

Results: Greater wake after sleep onset time measured with actigraphy (i.e., sleep disruption) (P = .01), loss of visual acuity (P = .009), and nonemployment/student status (P = .002) were all significant predictors of reduced daytime average total activity counts in a multiple linear regression model, after adjusting for contrast sensitivity as a cooperative suppressor variable (P = .01) (R = 0.54). Fragmentation measured with actigraphy (i.e., restlessness during sleep) (P = .07) and decreased sleep quality ratings reported upon awakening by the participants in a sleep diary (P = .06) were each marginally associated with reduced daytime average total activity counts, whereas nonemployment/student status, reduced visual acuity, and contrast sensitivity were still significant predictors. Objective and subjective measures of sleep or daytime activity were not statistically significantly correlated (P > .05).

Conclusions: We find nonemployment/student status and sleep disturbances appear to be related to reduced daytime activity levels in adults with central vision loss due to RP. These findings underscore the importance of developing and evaluating interventions to help RP patients maintain engagement in productive activities and improve their disturbed sleep.
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http://dx.doi.org/10.1097/OPX.0000000000001265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121737PMC
September 2018

Use of Actigraphy for the Evaluation of Sleep Disorders and Circadian Rhythm Sleep-Wake Disorders: An American Academy of Sleep Medicine Systematic Review, Meta-Analysis, and GRADE Assessment.

J Clin Sleep Med 2018 07 15;14(7):1209-1230. Epub 2018 Jul 15.

Saint Thomas Medical Partners-Sleep Specialists, Nashville, Tennessee.

Introduction: The purpose of this systematic review is to provide supporting evidence for a clinical practice guideline on the use of actigraphy.

Methods: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of actigraphy, sleep logs, and/or polysomnography. Statistical analyses were performed to determine the clinical significance of using actigraphy as an objective measure of sleep and circadian parameters. Finally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations.

Results: The literature search resulted in 81 studies that met inclusion criteria; all 81 studies provided data suitable for statistical analyses. These data demonstrate that actigraphy provides consistent objective data that is often unique from patient-reported sleep logs for some sleep parameters in adult and pediatric patients with suspected or diagnosed insomnia, circadian rhythm sleep-wake disorders, sleep-disordered breathing, central disorders of hypersomnolence, and adults with insufficient sleep syndrome. These data also demonstrate that actigraphy is not a reliable measure of periodic limb movements in adult and pediatric patients. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations.
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http://dx.doi.org/10.5664/jcsm.7228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040804PMC
July 2018

Use of Actigraphy for the Evaluation of Sleep Disorders and Circadian Rhythm Sleep-Wake Disorders: An American Academy of Sleep Medicine Clinical Practice Guideline.

J Clin Sleep Med 2018 07 15;14(7):1231-1237. Epub 2018 Jul 15.

Saint Thomas Medical Partners-Sleep Specialists, Nashville, Tennessee.

Introduction: The purpose of this guideline is to establish clinical practice recommendations for the use of actigraphy in adult and pediatric patients with suspected or diagnosed sleep disorders or circadian rhythm sleep-wake disorders.

Methods: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assigned strengths based on a systematic review of the literature and an assessment of the evidence using the GRADE process. The task force provided a summary of the relevant literature and the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations.

Recommendations: The following recommendations are intended as a guide for clinicians using actigraphy in evaluating patients with sleep disorders and circadian rhythm sleep-wake disorders, and only apply to the use of FDA-approved devices. Each recommendation statement is assigned a strength ("Strong" or "Conditional"). A "Strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "Conditional" recommendation (ie, "We suggest…") reflects a lower degree of certainty regarding the outcome and appropriateness of the patient-care strategy for all patients. The ultimate judgment regarding any specific care must be made by the treating clinician and the patient, taking into consideration the individual circumstances of the patient, available treatment options, and resources. We suggest that clinicians use actigraphy to estimate sleep parameters in adult patients with insomnia disorder. (Conditional). We suggest that clinicians use actigraphy in the assessment of pediatric patients with insomnia disorder. (Conditional). We suggest that clinicians use actigraphy in the assessment of adult patients with circadian rhythm sleep-wake disorder. (Conditional). We suggest that clinicians use actigraphy in the assessment of pediatric patients with circadian rhythm sleep-wake disorder. (Conditional). We suggest that clinicians use actigraphy integrated with home sleep apnea test devices to estimate total sleep time during recording (in the absence of alternative objective measurements of total sleep time) in adult patients suspected of sleep-disordered breathing. (Conditional). We suggest that clinicians use actigraphy to monitor total sleep time prior to testing with the Multiple Sleep Latency Test in adult and pediatric patients with suspected central disorders of hypersomnolence. (Conditional). We suggest that clinicians use actigraphy to estimate total sleep time in adult patients with suspected insufficient sleep syndrome. (Conditional). We recommend that clinicians use actigraphy in place of electromyography for the diagnosis of periodic limb movement disorder in adult and pediatric patients. (Strong).
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http://dx.doi.org/10.5664/jcsm.7230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040807PMC
July 2018

Exploring the Role of Negative Cognitions in the Relationship Between Ethnicity, Sleep, and Pain in Women With Temporomandibular Joint Disorder.

J Pain 2018 11 8;19(11):1342-1351. Epub 2018 Jun 8.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine. Baltimore, Maryland.

Negative cognitions are central to the perpetuation of chronic pain and sleep disturbances. Patients with temporomandibular joint disorder (TMJD), a chronic pain condition characterized by pain and limitation in the jaw area, have a high comorbidity of sleep disturbances that possibly exacerbate their condition. Ethnic group differences are documented in pain, sleep, and coping, yet the mechanisms driving these differences are still unclear, especially in clinical pain populations. We recruited 156 women (79% white, 21% African American) diagnosed with TMJD as part of a randomized, controlled trial evaluating the effectiveness of interventions targeting sleep and pain catastrophizing on pain in TMJD. Analysis of baseline data demonstrated that, relative to white participants, African Americans exhibited higher levels of clinical pain, insomnia severity, and pain catastrophizing, yet there was no ethnic group difference in negative sleep-related cognitions. Mediation models revealed pain catastrophizing, but not sleep-related cognitions or insomnia severity, to be a significant single mediator of the relationship between ethnicity and clinical pain. Only the helplessness component of catastrophizing together with insomnia severity sequentially mediated the ethnicity-pain relationship. These findings identify pain catastrophizing as a potentially important link between ethnicity and clinical pain and suggest that interventions targeting pain-related helplessness could improve both sleep and pain, especially for African American patients. Perspective:Pain-related helplessness and insomnia severity contribute to ethnic differences found in clinical pain among woman with TMJD. Findings can potentially inform interventions that target insomnia and catastrophizing to assist in reducing ethnic disparities in clinical pain.
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http://dx.doi.org/10.1016/j.jpain.2018.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215500PMC
November 2018

Elevated blood pressure in the developing world: a role for clinical pharmacists.

Int J Pharm Pract 2018 Aug 19;26(4):334-340. Epub 2017 Sep 19.

Wegmans School of Pharmacy, St. John Fisher College, Rochester, NY, USA.

Objective: The objective of this study was to evaluate the prevalence and patient knowledge of elevated blood pressure amongst a cross-section of patients in underserved communities in three selected low-income countries worldwide: El Salvador, India and Kenya.

Methods: Mobile medical clinics were established as part of medical mission trips in El Salvador, India and Kenya. Willing male and female patients, at least 25 years of age, who presented at each clinic were screened for elevated blood pressure, including 332 patients in El Salvador, 847 patients in India and 160 patients in Kenya. Patients were classified into Stage I or II elevated blood pressure based on modified JNCVII guidelines. A questionnaire was completed regarding their knowledge about the existence and management of their disease state.

Key Findings: Of the 1339 patients screened, 368 presented with elevated blood pressure (27%). Of these patients, 147 had been previously informed of hypertension or an elevated blood pressure (39.9%), 28 reported receiving antihypertensive medication (7.6%) and 24 reported awareness of non-pharmaceutical treatment options (6.5%). In Kenya, 81 patients were screened in a rural setting and 79 in an urban setting. Patients demonstrating controlled blood pressure were 63 (78%) and 38 (48%), respectively, demonstrating a significant difference between the rural versus urban settings (P = 0.00359).

Conclusions: All regions demonstrated similar trends in the prevalence of elevated blood pressure, highlighting the need for increased disease state education in these regions.
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http://dx.doi.org/10.1111/ijpp.12398DOI Listing
August 2018

Sex moderates the effects of positive and negative affect on clinical pain in patients with knee osteoarthritis.

Scand J Pain 2017 07 19;16:66-73. Epub 2017 Apr 19.

Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, United States.

Background And Aims: Sex differences in clinical pain severity and response to experimental pain are commonly reported, with women generally showing greater vulnerability. Affect, including state (a single rating) and stable (average daily ratings over two weeks) positive affect and negative affect has also been found to impact pain sensitivity and severity, and research suggests that affect may modulate pain differentially as a function of sex. The current study aimed to examine sex as a moderator of the relationships between affect and pain-related outcomes among participants with knee osteoarthritis (KOA).

Methods: One hundred and seventy-nine participants (59 men) with KOA completed electronic diaries assessing clinical pain, positive affect, and negative affect. A subset of participants (n=120) underwent quantitative sensory testing, from which a single index of central sensitization to pain was derived. We used multiple regression models to test for the interactive effects of sex and affect (positive versus negative and stable versus state) on pain-related outcomes. We used mixed effects models to test for the moderating effects of sex on the relationships between state affect and pain over time.

Results: Sex differences in affect and pain were identified, with men reporting significantly higher stable positive affect and lower central sensitization to pain indexed by quantitative sensory testing, as well as marginally lower KOA-specific clinical pain compared to women. Moreover, there was an interaction between stable positive affect and sex on KOA-specific clinical pain and average daily non-specific pain ratings. Post hoc analyses revealed that men showed trends towards an inverse relationship between stable positive affect and pain outcomes, while women showed no relationship between positive affect and pain. There was also a significant interaction between sex and stable negative affect and sex on KOA-specific pain such that men showed a significantly stronger positive relationship between stable negative affect and KOA-specific pain than women. Sex did not interact with state affect on pain outcomes.

Conclusions: Findings suggest that men may be particularly sensitive to the effects of stable positive affect and negative affect on clinical pain. Future work with larger samples is needed in order to identify potential mechanisms driving the sex-specific effects of affect on pain.

Implications: The current study provides novel data that suggesting that the association of positive affect, negative affect, and pain are different in men versus women with KOA. Further understanding of the difference in affective expression between men and women may lead to the development of novel therapeutic interventions and help to identify additional modifiable factors in the prevention and management of pain.
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http://dx.doi.org/10.1016/j.sjpain.2017.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576503PMC
July 2017

Sleep continuity, architecture and quality among treatment-seeking cannabis users: An in-home, unattended polysomnographic study.

Exp Clin Psychopharmacol 2017 08;25(4):295-302

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University.

The objective of the study was to describe self-report and objectively measured sleep characteristics of adult treatment-seeking cannabis users. Study participants (n = 87) were adults who were screened for a 12-week outpatient cannabis treatment research program in Baltimore, MD. Participants completed objective and self-report measures of sleep quality. Data were analyzed for the sample overall and after stratifying by sex (54 men, 33 women). Participants were primarily urban, socioeconomically disadvantaged African Americans. Participants were frequent, heavy cannabis users; among a subset of participants assessed, 76.7% used cannabis on the day/night of the assessment. Participants had low rates of other substance abuse and of psychiatric comorbidities. Polysomnography indicated 19.5% of participants received the recommended 7 to 9 hr of sleep, with women averaging more sleep than men. One third (31.0%) had sleep latencies >30 min, one half spent >30 min awake after sleep onset, and more than one half of the sample (55.2%) had sleep efficiency scores of <85%. Most participants met criteria for subthreshold (36.8%) or clinical insomnia (25.3%) on the Insomnia Severity Index, 77.0% had scores of >5 on the Pittsburgh Sleep Quality Index. Most had average scores on the Dysfunctional Beliefs and Attitudes About Sleep (DBAS) questionnaire (M = 51.1, SD = 18.8) that were higher than average among clinical insomnia patients. Women had higher DBAS scores than men. Most participants exhibited characteristics of disordered sleep, and sex differences were observed on polysomnography and self-report measures. Findings extend prior research concerning the association between cannabis use and disordered sleep. Data presented in this article come from Clinical Trial NCT01685073. (PsycINFO Database Record
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http://dx.doi.org/10.1037/pha0000126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309181PMC
August 2017

Psychological interventions that target sleep reduce pain catastrophizing in knee osteoarthritis.

Pain 2017 Nov;158(11):2189-2195

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Pain catastrophizing is a significant risk factor for patients with knee osteoarthritis (KOA) and thus is a target for many psychological interventions for pain. This study examined if interventions targeting sleep found to be effective in improving sleep in KOA also reduce pain catastrophizing measured as a trait through the pain catastrophizing scale and measured as a daytime and nocturnal state through daily diaries. Secondary analyses were conducted on data collected as part of a randomized controlled trial assessing the effectiveness of cognitive behavioral therapy for insomnia in patients with KOA at 5 different time points: pretreatment, midtreatment and posttreatment and at 3- and 6-month follow-up. One hundred patients diagnosed with KOA and insomnia were randomized to receive either 8 sessions of cognitive behavioral therapy for insomnia or a placebo intervention of behavioral desensitization. Multilevel modeling revealed that both intervention groups showed a significant reduction pretreatment to posttreatment in all 3 measures of pain catastrophizing and maintained stable levels through the 6-month follow-up. Increased sleep continuity early in treatment (pretreatment to midtreatment), but not reductions in pain, was associated with a reduction in trait and nocturnal catastrophizing later in treatment (midtreatment to posttreatment). These results suggest that short interventions focusing on sleep can significantly reduce pain catastrophizing even in a clinical population with low baseline levels of catastrophizing, possibly through improving sleep continuity.
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http://dx.doi.org/10.1097/j.pain.0000000000001023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640483PMC
November 2017

To take or not to take: the association between perceived addiction risk, expected analgesic response and likelihood of trying novel pain relievers in self-identified chronic pain patients.

Addiction 2018 Jan 10;113(1):67-79. Epub 2017 Aug 10.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background And Aims: Probability discounting refers to the effect of outcome uncertainty on decision making. Using probability discounting, we examined the degree to which self-identified chronic pain patients (CPP) were likely to try a novel analgesic medication given increasing addiction risk. We postulated that propensity for opioid misuse, trait impulsivity and previous opioid experience would be associated positively with likelihood of risky medication use.

Design: This cross-sectional on-line study determined state/trait associations with addiction-related medication decisions in CPP.

Setting: US-based CPP participated via Amazon Mechanical Turk; data were collected and analyzed in Baltimore, Maryland.

Participants: A total of 263 CPP (70.6% female) participated in the study from 12-13 December 2014.

Measurements: CPP responded to the Benefit versus Addiction Risk Questionnaire (BARQ) assessing likelihood of taking a hypothetical once-daily oral analgesic medication as a function of two factors: risk of addiction (0-50%) and duration of expected complete pain relief (3, 30 or 365 days). The primary outcome was the BARQ, quantified as area under the curve (AUC). Grouping of CPP at high or low risk for opioid misuse was based on the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R). Predictors included previous experience with opioids, as well as various measures of chronic pain and mental health.

Findings: Across hypothetical addiction risk assessed in the BARQ, the likelihood of taking a novel analgesic medication was elevated significantly in patients with high (≥18; n = 137) versus low (<18; n = 126) SOAPP-R scores [P < 0.001; 3-day: Cohen's d = 0.66, 95% confidence interval (CI) = 0.63, 0.69; 30-day: d = 0.74, 95% CI = 0.71, 0.78; 365-day: d = 0.75, 95% CI = 0.72, 0.79].

Conclusions: In the United States, self-identified chronic pain patients (CPP) at higher risk for opioid misuse were more likely to report willingness to try a novel analgesic despite increasing addiction risk than CPP with low risk of opioid misuse.
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http://dx.doi.org/10.1111/add.13922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725253PMC
January 2018

Mid-Treatment Sleep Duration Predicts Clinically Significant Knee Osteoarthritis Pain reduction at 6 months: Effects From a Behavioral Sleep Medicine Clinical Trial.

Sleep 2017 Feb;40(2)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine,Baltimore, MD.

Study Objectives: To determine the relative influence of sleep continuity (sleep efficiency, sleep onset latency, total sleep time [TST], and wake after sleep onset) on clinical pain outcomes within a trial of cognitive behavioral therapy for insomnia (CBT-I) for patients with comorbid knee osteoarthritis and insomnia.

Methods: Secondary analyses were performed on data from 74 patients with comorbid insomnia and knee osteoarthritis who completed a randomized clinical trial of 8-session multicomponent CBT-I versus an active behavioral desensitization control condition (BD), including a 6-month follow-up assessment. Data used herein include daily diaries of sleep parameters, actigraphy data, and self-report questionnaires administered at specific time points.

Results: Patients who reported at least 30% improvement in self-reported pain from baseline to 6-month follow-up were considered responders (N = 31). Pain responders and nonresponders did not differ significantly at baseline across any sleep continuity measures. At mid-treatment, only TST predicted pain response via t tests and logistic regression, whereas other measures of sleep continuity were nonsignificant. Recursive partitioning analyses identified a minimum cut-point of 382 min of TST achieved at mid-treatment in order to best predict pain improvements 6-month posttreatment. Actigraphy results followed the same pattern as daily diary-based results.

Conclusions: Clinically significant pain reductions in response to both CBT-I and BD were optimally predicted by achieving approximately 6.5 hr sleep duration by mid-treatment. Thus, tailoring interventions to increase TST early in treatment may be an effective strategy to promote long-term pain reductions. More comprehensive research on components of behavioral sleep medicine treatments that contribute to pain response is warranted.
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http://dx.doi.org/10.1093/sleep/zsw064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251549PMC
February 2017

Partial Sleep Deprivation Attenuates the Positive Affective System: Effects Across Multiple Measurement Modalities.

Sleep 2017 Jan;40(1)

Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine, Baltimore, MD.

Objective: Ample behavioral and neurobiological evidence links sleep and affective functioning. Recent self-report evidence suggests that the affective problems associated with sleep loss may be stronger for positive versus negative affective state and that those effects may be mediated by changes in electroencepholographically measured slow wave sleep (SWS). In the present study, we extend those preliminary findings using multiple measures of affective functioning.

Design: In a within-subject randomized crossover experiment, we tested the effects of one night of sleep continuity disruption via forced awakenings (FA) compared to one night of uninterrupted sleep (US) on three measures of positive and negative affective functioning: self-reported affective state, affective pain modulation, and affect-biased attention.

Setting: The study was set in an inpatient clinical research suite.

Participants: Healthy, good sleeping adults (N = 45) were included.

Measurement And Results: Results indicated that a single night of sleep continuity disruption attenuated positive affective state via FA-induced reductions in SWS. Additionally, sleep continuity disruption attenuated the inhibition of pain by positive affect as well as attention bias to positive affective stimuli. Negative affective state, negative affective pain facilitation, nor negative attention bias were altered by sleep continuity disruption.

Conclusions: The present findings, observed across multiple measures of affective function, suggest that sleep continuity disruption has a stronger influence on the positive affective system relative to the negative affective affective system.
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http://dx.doi.org/10.1093/sleep/zsw017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084750PMC
January 2017