Claudia Campbell

Determine the degree of congruence between several measures of adverse events. Cross-sectional study to assess frequency and type of adverse events identified using a variety of methods. Mayo Clinic Rochester hospitals. All inpatients discharged in 2005 (n = 60 599). Adverse events were identified through multiple methods: (i) Agency for Healthcare Research and Quality-defined patient safety indicators (PSIs) using ICD-9 diagnosis codes from administrative discharge abstracts, (ii) provider-reported events, and (iii) Institute for Healthcare Improvement Global Trigger Tool with physician confirmation. PSIs were adjusted to exclude patient conditions present at admission. Agreement of identification between methods. About 4% (2401) of hospital discharges had an adverse event identified by at least one method. Around 38% (922) of identified events were provider-reported events. Nearly 43% of provider-reported adverse events were skin integrity events, 23% medication events, 21% falls,...

Robust interindividual variation in pain sensitivity has been observed, and recent evidence suggests that some of the variability may be genetically mediated. Our previous data revealed significantly higher pressure pain thresholds among individuals possessing the minor G allele of the A118G SNP of the mu-opioid receptor gene (OPRM1) compared with those with 2 consensus alleles. Moreover, ethnic differences in pain sensitivity have been widely reported. Yet, little is known about the potential interactive associations of ethnicity and genotype with pain perception. This study aimed to identify ethnic differences in OPRM1 allelic associations with experimental pain responses. A total of 247 healthy young adults from three ethnic groups (81 African Americans; 79 non-white Hispanics; and 87 non-Hispanic whites) underwent multiple experimental pain modalities (thermal, pressure, ischemic, cold pressor). Few African Americans (7.4%) expressed the rare allele of OPRM1 compared to non-Hispanic whites and Hispanics (28.7% vs. 27.8%, respectively). Across the entire sample, OPRM1 genotype did not significantly affect pain sensitivity. However, analysis in each ethnic group separately revealed significant genotype effects for most pain modalities among non-Hispanic-whites (P<.05) but not Hispanics or African Americans. The G allele was associated with decreased pain sensitivity among whites only; a trend in the opposite direction emerged in Hispanics. The reasons for this dichotomy are unclear; they may involve ethnic differences in haplotypic structure, or A118G may be a tag-SNP linked to other functional polymorphisms. These findings demonstrate an ethnicity-dependent association of OPRM1 genotype with pain sensitivity. Additional research is warranted to uncover the mechanisms influencing these relationships.

Sleep quality and ethnicity are related to a host of general health outcomes including the experience of pain, yet it remains unclear whether poor sleep quality and ethnicity might interactively affect pain catastrophizing and laboratory-evoked acute pain reports. The current study examined the cross-sectional associations of subjective sleep quality, ethnicity, and their interaction with pain catastrophizing and pain reports. Healthy (N = 149), ethnically diverse (58% Caucasian American, 23% Asian American, 19% African American) young adults were subjected to a cold pressor task (CPT). Prior to CPT, participants completed the Pittsburgh Sleep Quality Index and a standard version of the Pain Catastrophizing Scale (PCS). Following CPT, participants completed a situation-specific version of the PCS. Adjusted analyses revealed a significant sleep quality by ethnicity interaction for standard catastrophizing reports. Particularly, African Americans with poor overall sleep quality report...

A growing body of literature suggests that the experience of clinical pain differs across ethnocultural groups. Additionally, some evidence indicates greater sensitivity to experimentally induced pain among African Americans; however, most studies have included only one pain modality. This study examined ethnic differences in responses to multiple experimental pain stimuli, including heat pain, cold pressor pain, and ischemic pain. Heat pain threshold and tolerance, ratings of repetitive suprathreshold heat, and ischemic and cold pressor pain threshold and tolerance were assessed in 120 (62 African American, 58 white) healthy young adults. Also, several psychological instruments were administered. No ethnic group differences emerged for threshold measures, but African Americans had lower tolerances for heat pain, cold pressor pain and ischemic pain compared to whites. Ratings of intensity and unpleasantness for suprathreshold heat stimuli were significantly higher among African Americans. African Americans reported greater use of passive pain coping strategies and higher levels of hypervigilance. Controlling for passive pain coping did not account for group differences in pain responses, while controlling for hypervigilance rendered group differences in heat pain tolerance and ischemic pain tolerance non-significant. These findings demonstrate differences in laboratory pain responses between African Americans and whites across multiple stimulus modalities, and effect sizes for these differences in pain tolerance were moderate to large for suprathreshold measures. Hypervigilance partly accounted for group differences. Additional research to determine the mechanisms underlying these effects is warranted.

Identifying individual differences in pain is an important topic; however, little is known regarding patterns of responses across various experimental pain modalities. This study evaluated subgroups emerging from multiple experimental pain measures. One hundred and eighty-eight individuals (59.0% female) completed several psychological instruments and underwent ischemic, pressure, and thermal pain assessments. Thirteen separate pain measures were obtained by using three experimental pain modalities with several parameters tested within each modality. The pain ratings and scores were submitted to factor analysis that identified four pain factors from which Pain Sensitivity Index (PSI) scores were computed: heat pain (HP), pressure pain (PP), ischemic pain (IP), and temporal summation of heat pain (TS). Cluster analyses of PSI scores revealed four distinct clusters. The first cluster demonstrated high overall pain sensitivity, the second cluster revealed high TS, the third cluster showed particular insensitivity to IP and low sensitivity across pain modalities except PP, and the fourth cluster demonstrated low sensitivity to PP. Significant correlations were found between psychological measures and Index scores and those differed by sex. Cluster membership was associated with demographic variables of ethnicity and sex as well as specific psychosocial variables, although cluster differences were only partially explained by such factors. These analyses revealed that groups respond differently across varied pain stimuli, and this was not related solely to demographic or psychosocial factors. These findings highlight the need for future investigation to identify patterns of responses across different pain modalities in order to more accurately characterize individual differences in responses to experimental pain.

Many attempts to identify hospital complications rely on secondary diagnoses from billing data. To be meaningful, diagnosis codes must distinguish between diagnoses after admission and those existing before admission. To assess the influence of diagnoses at admission on patient safety, comorbidity, severity measures, and case mix groupings for Medicare reimbursement. Cross-sectional association of various diagnosis-based clinical and performance measures with and without diagnosis present on admission. Hospital discharges from Mayo Clinic Rochester hospitals in 2005 (N = 60,599). All hospital inpatients including surgical, medical, pediatric, maternity, psychiatric, and rehabilitation patients. About 33% of patients traveled more than 120 miles for care. Hospital patient safety indicators, comorbidity, severity, and case mix measures with and without diagnoses present at admission. Over 90% of all diagnoses were present at admission whereas 27.1% of all inpatients had a secondary diagnosis coded in-hospital. About one-third of discharges with a safety indicator were flagged because of a diagnosis already present at admission, more likely among referral patients. In contrast, 87% of postoperative hemorrhage, 22% of postoperative hip fractures, and 54% of foreign bodies left in wounds were coded as in-hospital conditions. Severity changes during hospitalization were observed in less than 8% of discharges. Slightly over 3% of discharges were assigned to higher weight diagnosis-related groups based on an in-hospital complication. In general, many patient safety indicators do not reliably identify adverse hospital events, especially when applied to academic referral centers. Except as noted, conditions recorded after admission have minimal impact on comorbidity and severity measures or on Medicare reimbursement.

Explore effects of comorbidity and prior health care utilization on choice of employee health plans with different levels of cost sharing. Mayo Clinic employees in Rochester, Minnesota (MCR) under age 65 in January 2004; N = 20,379. Assessment of a natural experiment where self-funded medical care benefit options were changed to contain costs within a large medical group practice. Before the change, most employees were enrolled in a plan with first dollar coverage, while 18% had a plan with copays and deductibles. In 2004, 3 existing plans were replaced by 2 new options, one with lower premiums and higher out-of-pocket costs and the other with higher premiums, a lower coinsurance rate, and lower out-of-pocket maximums. Data on employees were merged across insurance claims, medical records, eligibility files, and employment files for 2003 and 2004. As the number of chronic comorbidities among family members increased, the probability of choosing high-premium option also increased. Seventy-two percent of employees with at least 1 family member with comorbidity chose the high-cost option versus 54.7% of employees with no comorbidities. High-premium and low-premium plans seem to subdivide population into discrete risk categories, which may adversely affect the future stability of the insurance plan options. Various factors affect decision making of employees regarding the choice of plan with different levels of cost-sharing. In a natural experiment setting where all options were redesigned, the health status of employees and their dependents played a very significant role in plan choice.

Responses to painful stimuli are characterized by tremendous interindividual variability, and genetic factors likely account for some proportion of this variability. However, few studies have identified genetic contributions to experimental pain perception in humans. This experiment investigated whether the A118G single nucleotide polymorphism of the mu-opioid receptor gene ( OPRM1 ) was associated with responses to three different experimental pain modalities in a sample of 167 healthy volunteers (96 female, 71 male). Responses to thermal, mechanical, and ischemic pain were assessed in all subjects, and genotyping of OPRM1 was performed, which revealed that the rare A118G allele occurred in 24 females (25%) and 12 males (17%). Statistical analyses indicated that subjects with a rare allele had significantly higher pressure pain thresholds than those homozygous for the common allele. Also, a sex by genotype interaction emerged for heat pain ratings at 49 degrees C, such that the rare allele was associated with lower pain ratings among men but higher pain ratings among women. These data indicate an association of a common single nucleotide polymorphism of OPRM1 with mechanical pain responses and that this genotype may be associated with heat pain perception in a sex-dependent manner. This study examines the association of the A118G SNP of OPRM1 to experimental pain sensitivity. The results indicate that the rare allele is associated with higher pressure pain thresholds. These results support previous contentions that OPRM1 may be a pain-relevant gene; however, replication of these findings is needed.

Sex differences in analgesic responses to mu opioid agonists have been reported, although the direction of these differences varies across studies. To further characterize sex differences in responses to mu opioids, the analgesic effects of intravenous morphine (0.08 mg/kg) were determined in healthy women (n = 61) and men (n = 39) by using 3 experimental pain models, heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both morphine and saline, which occurred on separate days in counterbalanced order. Although morphine produced significant analgesic effects for all pain stimuli, no significant sex differences in morphine analgesia emerged. However, morphine attenuated cardiovascular reactivity to the ischemic pain task in men but not women, and women reported significantly more drug-related adverse effects than men. These findings are in contrast with some recent clinical and experimental results suggesting more robust analgesic response to mu opioids among women compared to men, although the data indicate that sex differences in non-analgesic effects of morphine were present. These results suggest that sex differences in responses to morphine might depend on the pain model and/or drug dose as well as the specific end point assessed. This study examines morphine responses in women and men by using laboratory pain measures. The results indicate no sex differences in analgesia, but women reported greater side effects, and morphine attenuated cardiovascular responses more strongly among men than women. These results add to the literature regarding sex differences in response to opioids.

ABSTRACT Taste perception is an area of increasing attention, as it has recently been associated with long-term health implications such as alcohol intake and cardiovascular disease. Ethnic variations in taste perception have been observed, generally suggesting a preference for sweet tastes in African American participants. The mechanisms underlying taste preference are unclear, though involvement of the endogenous opioid system has been hypothesized. Limited research has examined this connection, though the extant literature suggests individual differences in pressure pain and cold pressor pain tolerance following ingestion of sweet liquid, thus providing evidence for "palatability-induced antinociception." Ethnic differences in response to both clinical and experimentally induced pain have been well documented and recent evidence may suggest variability in descending inhibition. In the current study we examined the relationship between taste perception and pain responses associated with endogenous opioid activation, the nociceptive flexion reflex (NFR) and diffuse noxious inhibitory controls (DNIC, using NFR and ischemic arm pain) among healthy African Americans (N=22) and non-Hispanic whites (N=24). Four solutions, salty, sweet, sour, and bitter, were applied to the tongue, intensity of the taste sensation was rated immediately following each swab. No ethnic differences in taste ratings emerged. Significant correlations between taste sensitivity and pain were observed. Ratings of sweet and bitter predicted NFR threshold among whites, with higher taste ratings predicting higher NFR; no such association was evident in African Americans. However, ratings of sweet and bitter predicted DNIC-induced reductions in the NFR reflex in both African Americans and whites, with higher taste ratings predicting greater pain inhibition. One potential explanation for these findings is that perception of taste is mediated in part through brain systems (e.g. endogenous opioids) that also influence pain. Thus, measurement of taste sensitivity may reflect the integrity of those systems. Possible underlying mechanisms and potential clinical implications will be discussed.

To examine the predictors of duloxetine monotherapy versus other antidepressants among patients with major depressive disorder (MDD) in the Veterans Health Administration (VHA). Patients initiating duloxetine or other antidepressants between October 1, 2005 and October 1, 2007 were extracted from the Veterans Integrated Service Network (VISN)16 data warehouse. All patients included had at least one MDD diagnosis prior to the initiation of duloxetine or other antidepressants. Patients with prior diabetes, schizophrenia, or bipolar disorder diagnosis were excluded. Logistic regression was used to identify predictors of duloxetine initiation versus other antidepressants. Among 448 duloxetine and 11,629 non-duloxetine patients identified, more duloxetine-treated patients had pre-index opioid use (62.72% vs. 22.03%), substance abuse (36.38% vs. 27.72%), or reported pain (60.94% vs. 46.29%) than non-duloxetine treated patients (all p-values <0.001). Prior users of long-acting (odds ratio [OR] = 8.98, 95% confidence interval [CI]: 6.95, 11.60) and short-acting (OR = 3.32, 95% CI: 2.60, 4.23) opioids were more likely to initiate duloxetine than those not. Patients who experienced moderate or severe pain or substance abuse were also more likely to initiate duloxetine (OR = 1.43, 95% CI: 1.07, 1.90; 1.50, 95% CI: 1.16, 1.92; 1.41, 95% CI: 1.14, 1.75; respectively). Other significant predictors included being female, white, having non-VHA insurance, prior hospitalization, emergency room visits, dyslipidemia and hypertension (all p-values <0.05). It is a retrospective analysis among VHA patients of a single VISN. Among the VHA patients with MDD, prior opioid use was the strongest predictor of duloxetine initiation, followed by moderate-to-severe pain and substance abuse diagnosis.

Sex differences in pain perception and analgesic responses have garnered increasing attention in recent years. We examined the association of psychological factors to baseline pain perception and pentazocine analgesia among 49 healthy women and 39 men. Subjects completed psychological questionnaires measuring positive and negative affect as well as catastrophizing. Subsequently, responses to experimental pain were assessed before and after double-blind administration of intravenous pentazocine (0.5mg/kg). In correlational analyses, positive affect predicted lower pain sensitivity among men but not women. Negative affect predicted lower baseline pain tolerances among both sexes but predicted poorer analgesia only among men. Catastrophizing was associated with greater pain sensitivity and less analgesia more consistently in men than women. Regression models revealed that positive affect predicted lower overall pain sensitivity and catastrophizing predicted poorer overall analgesic responses among men, while no significant predictors of overall pain or analgesia emerged for women. Moreover, positive affect and catastrophizing were negatively and positively correlated, respectively, with side effects from the medication, but only among men. These findings indicate sex-dependent associations of psychological factors with baseline pain perception, analgesic responses, and medication side effects.

Accumulating evidence suggests that there are sex differences in analgesic responses to opioid agonists. Several studies using an oral surgery pain model have reported more robust analgesia to kappa-agonist-antagonists (e.g., pentazocine, nalbuphine, butorphanol) among women than among men. However, evidence of sex differences in kappa-agonist-antagonist effects from studies of experimentally induced pain in humans is lacking. Therefore, the analgesic effects of intravenous pentazocine (0.5 mg/kg) were determined in healthy women (n = 41) and men (n = 38) using three experimental pain models: heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both pentazocine and saline, which occurred on separate days in counterbalanced order. Compared with saline, pentazocine produced significant analgesic responses for all pain stimuli. However, no sex differences in pentazocine analgesia emerged. Effect sizes for the sex differences were computed; the magnitude of effects was small, and an equal number of measures showed greater analgesia in men than in women. Also, analgesic responses were not highly correlated across pain modalities, suggesting that different mechanisms may underlie analgesia for disparate types of pain. These findings indicate significant analgesic responses to pentazocine in both men and women across multiple experimental pain assays, and the absence of sex differences contrasts with previous data from the oral surgery model. The most likely explanation for the discrepancy in results is that of differences in the pain assays. These findings are important because they suggest that sex differences in opioid analgesia may be specific to certain types of pain.