The serial intervals of seasonal and pandemic influenza viruses in households in Bangkok, Thailand.

The serial interval (SI) of human influenza virus infections is often described by a single distribution. Understanding sources of variation in the SI could provide valuable information for understanding influenza transmission dynamics. Using data from a randomized household study of nonpharmaceutical interventions to prevent influenza transmission in Bangkok, Thailand, over 34 months between 2008 and 2011, we estimated the influence of influenza virus type/subtype and other characteristics of 251 pediatric index cases and their 315 infected household contacts on estimates of household SI. The mean SI for all households was 3.3 days. Relative to influenza A(H1N1)pdm09 (3.1 days), the SI for influenza B (3.7 days) was 22% longer (95% confidence interval: 4, 43), or about half a day. The SIs for influenza viruses A(H1N1) and A(H3N2) were similar to that for A(H1N1)pdm09. SIs were shortest for older index cases (age 11-14 years) and for younger infected household contacts (age ≤15 years). Greater time spent in proximity to the index child was associated with shorter SIs. Differences in the SI might reflect differences in incubation period, viral shedding, contact, or susceptibility. These findings could improve parameterization of mathematical models to better predict the impact of epidemic or pandemic influenza mitigation strategies.

Transmissibility of seasonal and pandemic influenza in a cohort of households in Hong Kong in 2009.

BACKGROUND: The household secondary attack proportion (SAP) is commonly used to measure the transmissibility of an infectious disease. METHODS: We analyzed the final outbreak size distributions of pandemic A(H1N1), seasonal A(H1N1), and A(H3N2) infections identified in paired sera collected from members of 117 Hong Kong households in April and in August-October 2009. RESULTS: The estimated community probability of infection overall was higher for children than adults; the probability was similar for pandemic A(H1N1) and seasonal A(H3N2) influenza. The household SAP for pandemic A(H1N1) was higher in children than in adults, whereas for seasonal A(H3N2), it was similar in children and adults. The estimated SAPs were similar for seasonal A(H3N2) and pandemic A(H1N1) after excluding persons with higher baseline antibody titers from analysis. CONCLUSIONS: Pandemic and seasonal influenza A viruses had similar age-specific transmissibility in a cohort of initially uninfected households, after adjustment for baseline immunity.

Sleep disorders and their association with laboratory pain sensitivity in temporomandibular joint disorder.

STUDY OBJECTIVES: We characterized sleep disorder rates in temporomandibular joint disorder (TMD) and evaluated possible associations between sleep disorders and laboratory measures of pain sensitivity. DESIGN: Research diagnostic examinations were conducted, followed by two consecutive overnight polysomnographic studies with morning and evening assessments of pain threshold. SETTING: Orofacial pain clinic and inpatient sleep research facility. PARTICIPANTS: Fifty-three patients meeting research diagnostic criteria for myofascial TMD. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: We determined sleep disorder diagnostic rates and conducted algometric measures of pressure pain threshold on the masseter and forearm. Heat pain threshold was measured on the forearm; 75% met self-report criteria for sleep bruxism, but only 17% met PSG criteria for active sleep bruxism. Two or more sleep disorders were diagnosed in 43% of patients. Insomnia disorder (36%) and sleep apnea (28.4%) demonstrated the highest frequencies. Primary insomnia (PI) (26%) comprised the largest subcategory of insomnia. Even after controlling for multiple potential confounds, PI was associated with reduced mechanical and thermal pain thresholds at all sites (P < 0.05). Conversely, the respiratory disturbance index was associated with increased mechanical pain thresholds on the forearm (P < 0.05). CONCLUSIONS: High rates of PI and sleep apnea highlight the need to refer TMD patients complaining of sleep disturbance for polysomnographic evaluation. The association of PI and hyperalgesia at a nonorofacial site suggests that PI may be linked with central sensitivity and could play an etiologic role in idiopathic pain disorders. The association between sleep disordered breathing and hypoalgesia requires further study and may provide novel insight into the complex interactions between sleep and pain-regulatory processes.

Catastrophizing and depressive symptoms as prospective predictors of outcomes following total knee replacement.

Several recent reports suggest that pain-related catastrophizing is a risk factor for poor acute pain outcomes following surgical interventions. However, it has been less clear whether levels of catastrophizing influence longer-term postoperative outcomes. Data were analyzed from a relatively small number (n=43) of patients who underwent total knee replacement and were followed for 12 months after their surgery. Previous research has suggested that high levels of both catastrophizing and depression are associated with elevated acute postoperative pain complaints among patients undergoing knee surgery. In this sample, catastrophizing and depression at each of the assessment points were studied as prospective predictors of pain (both global pain ratings and pain at night) at the subsequent assessment point over the course of one year. The predictive patterns differed somewhat across measures of pain reporting; depressive symptoms were unique predictors of greater global pain complaints, while catastrophizing was a specific and unique predictor of elevated nighttime pain. While surgical outcomes following total knee replacement are, on average, quite good, a significant minority of patients continue to experience long-term pain. The present findings suggest that high levels of catastrophizing and depression may promote enhanced pain levels, indicating that interventions designed to reduce catastrophizing and depressive symptoms may have the potential to further improve joint replacement outcomes.

Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial.

BACKGROUND: Stump and phantom pains are debilitating sequelae of amputations that are often resistant to treatment. The efficacy of pharmacologic therapies, including opioids and sodium channel blockers, for postamputation pain is uncertain. METHODS: The authors conducted a double-blind, randomized, placebo-controlled, crossover study in adult patients with postamputation pain of 6 months or longer and greater than 3 on a 0-10 numeric pain rating scale. Each of the three treatment periods (morphine, mexiletine, or placebo) included a 1-week drug-free interval followed by 4-week titration, 2-week maintenance, and 2-week drug-taper phases. The primary outcome measure was change in average pain intensity from the drug-free baseline to the last week of maintenance. RESULTS: Sixty amputees were enrolled; data were analyzed from 56 subjects for one drug period, 45 subjects for two drug periods, and 35 subjects who completed all three drug periods. The mean morphine and mexiletine dosages were 112 and 933 mg, respectively. Morphine treatment provided lower pain scores compared with placebo and mexiletine (P = 0.0003). The mean percent pain relief during treatment with placebo, mexiletine, and morphine was 19, 30, and 53%, respectively (P < 0.0001, morphine vs. placebo and mexiletine). The numbers needed to treat to obtain 50% and 33% decreases in pain intensity with morphine were 5.6 and 4.5, respectively. Treatment with morphine was associated with a higher rate of side effects. CONCLUSIONS: Therapy with morphine, but not mexiletine, resulted in a decrease in intensity of postamputation pain but was associated with a higher rate of side effects and no improvement in self-reported levels of overall functional activity and pain-related interference in daily activities.

Associations of patient health-related problem solving with disease control, emergency department visits, and hospitalizations in HIV and diabetes clinic samples.

BACKGROUND: Patient problem solving and decision making are recognized as essential to effective self-management across multiple chronic diseases. However, a health-related problem-solving instrument that demonstrates sensitivity to disease control parameters in multiple diseases has not been established. OBJECTIVES: To determine, in two disease samples, internal consistency and associations with disease control of the Health Problem-Solving Scale (HPSS), a 50-item measure with 7 subscales assessing effective and ineffective problem-solving approaches, learning from past experiences, and motivation/orientation. DESIGN: Cross-sectional study. PARTICIPANTS: Outpatients from university-affiliated medical center HIV (N = 111) and diabetes mellitus (DM, N = 78) clinics. MEASUREMENTS: HPSS, CD4, hemoglobin A1c (HbA1c), and number of hospitalizations in the previous year and Emergency Department (ED) visits in the previous 6 months. RESULTS: Administration time for the HPSS ranged from 5 to 10 minutes. Cronbach's alpha for the total HPSS was 0.86 and 0.89 for HIV and DM, respectively. Higher total scores (better problem solving) were associated with higher CD4 and fewer hospitalizations in HIV and lower HbA1c and fewer ED visits in DM. Health Problem-Solving Scale subscales representing negative problem-solving approaches were consistently associated with more hospitalizations (HIV, DM) and ED visits (DM). CONCLUSIONS: The HPSS may identify problem-solving difficulties with disease self-management and assess effectiveness of interventions targeting patient decision making in self-care.

Live attenuated seasonal and pandemic influenza vaccine in school-age children: a randomized controlled trial.

BACKGROUND: The novel influenza A(H1N1pdm09) virus emerged in North America in early 2009 and rapidly spread worldwide. In this study we report the efficacy of the live attenuated monovalent H1N1pdm09 vaccine and 2009-10 seasonal influenza vaccine in a randomized double-blind placebo-controlled trial. METHODS: We enrolled 703 children aged 7-11. Each child was randomly allocated in the ratio 3:2 to receive one dose of live attenuated monovalent H1N1pdm09 vaccine or saline placebo between November 2009 and January 2010, followed after 3-10 weeks by independent random allocation to one dose of live attenuated trivalent 2009-10 seasonal influenza vaccine or saline placebo in the same ratio. Children were followed up through September 2010 with biweekly telephone calls and symptom diaries. Seasonal and pandemic influenza infections were confirmed by virologic testing of nose and throat swabs collected during acute respiratory illnesses. RESULTS: Overall, 30 children had confirmed influenza including 3 (0.43%) H1N1pdm09, 10 (1.4%) seasonal A(H3N2), and 17 (2.4%) influenza B. There were no significant differences in incidence rates of H1N1pdm09 or A(H3N2) between the four study arms, but receipt of the seasonal influenza vaccine was associated with a significant reduction in risk of influenza B (p<0.01). Vaccine efficacy against confirmed H1N1pdm09 infection associated with receipt of the monovalent H1N1pdm09 vaccine was 65% (95% confidence interval, CI: -281%, 97%). Vaccine efficacies against confirmed seasonal influenza A(H3N2) and B infection associated with receipt of the seasonal influenza vaccine were 31% (95% CI: -138%, 80%) and 96% (95% CI: 67%, 99%) respectively. CONCLUSIONS: Vaccine efficacy was consistent with other studies of the monovalent H1N1pdm09 vaccine and seasonal influenza vaccines. Our study was underpowered to provide precise estimates of vaccine efficacy due to low incidence of influenza A viruses during the study period.

Optimal design of intervention studies to prevent influenza in healthy cohorts.

BACKGROUND: Influenza cohort studies, in which participants are monitored for infection over an epidemic period, are invaluable in assessing the effectiveness of control measures such as vaccination, antiviral prophylaxis and non-pharmaceutical interventions (NPIs). Influenza infections and illnesses can be identified through a number of approaches with different costs and logistical requirements. METHODOLOGY AND PRINCIPAL FINDINGS: In the context of a randomized controlled trial of an NPI with a constrained budget, we used a simulation approach to examine which approaches to measuring outcomes could provide greater statistical power to identify an effective intervention against confirmed influenza. We found that for a short epidemic season, the optimal design was to collect respiratory specimens at biweekly intervals, as well as following report of acute respiratory illness (ARI), for virologic testing by reverse transcription polymerase chain reaction (RT-PCR). Collection of respiratory specimens only from individuals reporting ARI was also an efficient design particularly for studies in settings with longer periods of influenza activity. Collection of specimens only from individuals reporting a febrile ARI was less efficient. Collection and testing of sera before and after influenza activity appeared to be inferior to collection of respiratory specimens for RT-PCR confirmation of acute infections. The performance of RT-PCR was robust to uncertainty in the costs and diagnostic performance of RT-PCR and serological tests. CONCLUSIONS AND SIGNIFICANCE: Our results suggest that unless the sensitivity or specificity of serology can be increased RT-PCR will remain as the preferable outcome measure in NPI studies. Routine collection of specimens for RT-PCR testing even when study participants do not report acute respiratory illness appears to be the most cost efficient design under most scenarios.

Posttraumatic stress disorder and pain impact functioning and disability after major burn injury.

This study sought to clarify the prospective and concurrent associations of posttraumatic stress disorder (PTSD) and pain with functioning and disability after burn injury. The sample was composed of consecutive patients admitted to a regional burn center with major burn injuries (N = 171) who were followed at 1, 6, 12, and 24 months postdischarge. The predictor measures were the McGill Pain Questionnaire and Davidson Trauma Scale, and the outcome measures were Short Form-36 Health Survey subscales administered at 6, 12, and 24 months after discharge. Linear mixed-effects analyses were conducted to evaluate pain and PTSD as predictors of functional outcomes. Higher PTSD symptom severity soon after hospital discharge was prospectively related to poorer physical and social functioning and greater psychosocial disability (P < .001). However, significant PTSD-by-time interactions also predicted future physical functioning and disability, indicating that the deleterious effects of early PTSD were ameliorated by time. In addition, at each follow-up, PTSD symptoms were concurrently related to greater physical and psychosocial disability, poorer social functioning, and less vitality (P < .001). More severe pain at each follow-up, but not PTSD, was correlated with poorer concurrent physical functioning (P < .002). Significant interaction terms indicated that the concurrent effect of PTSD on psychosocial disability, social functioning, and vitality attenuated during the 24-month recovery period. These findings suggest that assessing PTSD and pain following burn injury may aid in predicting future functioning. Future work should confirm this and evaluate whether aggressively treating both PTSD and pain helps improve functioning after major burn injury.

Formative experiences of emerging physicians: gauging the impact of events that occur during medical school.

PURPOSE: Emotional development, an important component of nascent professional competence, is likely to be shaped by specific formative experiences. This study sought to identify and gauge the impact of highly evocative experiences occurring during medical school. METHOD: A 34-item list of candidate formative experiences was developed through focus group meetings of "colleges program"-affiliated student-advising faculty. The resulting survey instrument was administered to 216 graduating medical students at the Johns Hopkins University School of Medicine in 2007 and 2008 in a cohort study. Primary outcomes were exposure rates for the experiences and students' ratings of impact for those that occurred. RESULTS: One hundred eighty-one students (84%) responded. All events were experienced by >25% of students. Two events were described by most as having tremendous impact: "finding an exceptional role model" and "identifying a perfect area of medicine." Other prevalent events with strong impact included "a special patient-care experience," "working well with a team," "seeing a patient whose life was saved," "encountering a negative role model," "seeing a patient die," "seeing a patient experience severe pain," and "a bad clinical experience." Factor analysis revealed three event clusters: "inspiring experiences," "mortality-related experiences," and "negative experiences relating to the learning environment." CONCLUSIONS: Specific formative experiences have especially strong impacts on medical students. Whereas the intrinsic value of such experiences should continue to drive educational design, increased awareness of the diversity and range of formative experiences will prepare educators to more effectively guide positive emotional development, enhancing personal and professional growth during medical school.

Pain catastrophizing and salivary cortisol responses to laboratory pain testing in temporomandibular disorder and healthy participants.

UNLABELLED: Pain catastrophizing is an important variable in the context of acute and chronic pain. The neurophysiological correlates of pain catastrophizing, however, have not been rigorously evaluated. We examined the relationship between trait-pain catastrophizing and morning salivary cortisol levels before and following a 45-minute laboratory pain-testing session in healthy, pain-free (n = 22), and temporomandibular disorder (TMD) participants (n = 39). We also examined whether TMD patients evidenced generalized hyperalgesia and hypercortisolism. Pain catastrophizing was associated with a flattened morning salivary cortisol profile in the context of pain testing, irrespective of pain status. Cortisol profiles did not differ between healthy and TMD participants. TMD was associated with mechanical hyperalgesia only at the masseter. These data are the first to show an association between pain catastrophizing and elevated salivary cortisol profiles in the context of standardized experimental pain testing. These findings in both healthy individuals and those with chronic orofacial pain suggest that aberrant adrenocortical responses to pain may serve as a neurophysiologic pathway by which pain catastrophizing enhances vulnerability for development of chronic pain and maintains and/or exaggerates existing pain and associated morbidity. PERSPECTIVE: Neurophysiological mechanisms by which pain catastrophizing is related to acute and chronic pain recently have come under empirical study. Understanding of these mechanisms has the unique potential to shed light on key central-nervous-system factors that mediate catastrophizing-pain relations and therapeutic benefits associated with changes in catastrophizing and related cognitive processes.

Naturalistic changes in insomnia symptoms and pain in temporomandibular joint disorder: a cross-lagged panel analysis.

An increasing number of prospective studies suggest a bi-directional association between the pain and sleep quality. Few of these investigations have controlled for synchronous correlations, an important source of extraneous variance in lagged associations, which may have confounded conclusions of prior investigations. Despite high rates of insomnia in temporomandibular joint disorders (TMD), no studies have examined temporal associations between naturalistic fluctuations in insomnia and pain in TMD. We conducted cross-lagged panel analysis to examine reciprocal temporal associations between 1-month changes in insomnia symptom severity and self-reported pain over 3 months among 53 TMD patients. This rigorous analytic strategy represents a comprehensive method to explore possible reciprocal temporal associations between insomnia and pain that controls for both auto- and synchronous correlations. Analyses revealed that initial-month increases in insomnia were associated with next-month increases in average daily pain, but not vice versa. The direction of the effect was such that initial-month increases in insomnia symptom severity were associated with next-month increases in average daily pain. These data suggest that naturally occurring fluctuations in insomnia symptom severity are prospectively associated with fluctuations in daily pain experience for persons with TMD. Potential mechanisms by which insomnia might influence pain in TMD and therapeutic implications of these findings are discussed.

Duration of sleep contributes to next-day pain report in the general population.

Cross-sectional research in clinical samples, as well as experimental studies in healthy adults, suggests that the experiences of pain and sleep are bi-directionally connected. However, whether sleep and pain experiences are prospectively linked to one another on a day-to-day basis in the general population has not previously been reported. This study utilizes data from a naturalistic, micro-longitudinal, telephone study using a representative national sample of 971 adults. Participants underwent daily assessment of hours slept and the reported frequency of pain symptoms over the course of one week. Sleep duration on most nights (78.0%) was between 6 and 9h, and on average, daily pain was reported with mild frequency. Results suggested that hours of reported sleep on the previous night was a highly significant predictor of the current day's pain frequency (Z=-7.9, p<.0001, in the structural equation model); obtaining either less than 6 or more than 9h of sleep was associated with greater next-day pain. In addition, pain prospectively predicted sleep duration, though the magnitude of the association in this direction was somewhat less strong (Z=-3.1, p=.002, in the structural equation model). Collectively, these findings indicate that night-to-night changes in sleep affect pain report, illuminating the importance of considering sleep when assessing and treating pain.

Sleep onset insomnia symptoms during hospitalization for major burn injury predict chronic pain.

Both cross-sectional studies of chronic pain and sleep deprivation experiments suggest a bi-directional relationship between sleep and pain. Few longitudinal studies, however, have assessed whether acute insomnia following traumatic injury predicts the development of persistent pain. We sought to evaluate (1) whether in-hospital insomnia independently predicts long-term pain after burn injury and (2) whether in-hospital pain predicts future insomnia symptoms. We analyzed data on 333 subjects hospitalized for major burn injury (72.7% male; mean age=41.1+/-14.5years) who were participating in the multi-site, Burn Model System project. Subjects completed measures of health, function (SF-36), and psychological distress (Brief Symptom Inventory) while in hospital, at 6, 12, and 24months after discharge. Participants were categorized as either having or not having sleep onset insomnia at discharge. Linear mixed effects analyses revealed that persons reporting insomnia at discharge (40.5%) had significantly decreased improvement in pain and increased pain severity during long-term follow-up (p<0.001). More severe pain during the week preceding hospital discharge, time from injury, lack of college education and older age also contributed independent effects on chronic pain (p<0.05). In a reciprocal model (N=299), more severe pain during the week preceding discharge predicted increased rates of long-term sleep onset insomnia. In-hospital insomnia and pre-burn mental health symptoms were also highly significant predictors of insomnia. This study provides support for a long-term, prospective and reciprocal interaction between insomnia and pain. Future work should ascertain whether treatment of insomnia and pain during acute injury can prevent or minimize chronic pain.

Symptoms of distress as prospective predictors of pain-related sciatica treatment outcomes.

Prior studies evaluating predictors of pain-related outcomes following treatment for sciatica have been limited by methodological problems, including retrospective study design, use of unvalidated outcome measures, and short-term follow-up periods. Despite these limitations, some reports have suggested that symptoms of psychological distress may predict individual differences in pain treatment-related outcomes (e.g., higher levels of depressive and anxious symptomatology are associated with greater pain and disability after treatment). In this study, we sought to determine whether acute symptoms of depression and anxiety were prospectively associated with treatment outcomes over a 3-year follow-up period in surgically treated and non-surgically treated patients with sciatica. Patients were recruited from the practices of community-based physicians throughout the state of Maine, and underwent in-person baseline assessments, with mailed follow-up questionnaires at 3, 6, 12, 24, and 36 months. Study outcomes included patient-reported symptoms of pain and disability. For each outcome variable, we examined whether baseline mood (i.e., mood assessed prior to the initiation of treatment), as well as mood at the immediately preceding assessment point, prospectively predicted outcomes over 3 years in multivariate repeated-measures analyses. In most analyses, symptoms of depression and anxiety, both at baseline and at the preceding time point, were significant independent predictors of worse pain and function after controlling for relevant covariates. Collectively, elevated distress appears to be a significant risk factor for reduced treatment benefit (i.e., less improvement in pain and disability) over short and medium-term follow-up periods in patients with sciatica. Future research should determine whether the prospective identification and treatment of patients with high levels of distress (a "yellow flag") is associated with improved treatment outcomes.

Symptoms of depression and anxiety as unique predictors of pain-related outcomes following burn injury.

BACKGROUND: The adverse consequences of burn injuries include pain and psychological distress, which show bidirectional associations. However, much of the existing research has relied on global measures of distress that do not separate distinct symptoms of anxiety and depression. PURPOSE: The purpose is to assess the prospective effects of anxiety and depression on pain and functional outcomes following burn injury. METHODS: This article describes a 2-year cohort study in patients hospitalized for serious burn injuries (assessments at discharge and 6-month, 1-year, and 2-year follow-up). Linear mixed effects analyses were conducted to model anxiety and depression's unique longitudinal effects; at each time point, depressive and anxiety symptoms were studied as predictors of subsequent changes in pain, fatigue, and physical function. RESULTS: When studied in separate prediction models, both depression and anxiety were strong prospective predictors of greater pain, more fatigue, and physical dysfunction at the subsequent time point (ps < .01). However, when both were included in a single model to study their unique effects, depressive symptoms (but not anxiety) emerged as a significant predictor of subsequent increases in pain and reductions in physical functioning, whereas anxiety (but not depression) predicted subsequent elevations in fatigue. CONCLUSIONS: These findings suggest potentially distinct effects of depression and anxiety and imply that assessment and early treatment of both depressive and anxiety symptoms may help improve a broad range of long-term pain-related outcomes following burn injury.