Trends of Low Back Pain Research in Older and Working-Age Adults from 1993 to 2023: A Bibliometric Analysis.

Although the number of publications focusing on low back pain in older adults (LBP-O) and working-age adults (LBP-W) has been growing for decades, comparative research trends in these two populations, which may help to guide future investigation, have not been rigorously explored. This analysis aimed to describe publication patterns and trends of research targeting LBP-O and LBP-W over the last three decades. Peer-reviewed LBP-O and LBP-W articles published between 1993 and 2023 were retrieved from the Web of Science, which provided the details of annual publication volume, and prominent journals/countries/institutions. The relationship between the annual publication volumes and years was analyzed by Spearman correlation analysis. The hot topics and emerging trends were analyzed by VOSviewer and CiteSpace, respectively. A total of 4217 LBP-O-related and 50,559 LBP-W-related documents were included. The annual publication volumes of LBP-O and LBP-W articles increased over the years (r=0.995 to 0.998, p<0.001). The United States had the highest number of prominent institutions publishing relevant articles. The most prolific journal for LBP-O (5.4%) and LBP-W-related (6.1%) papers is the journal "Spine". Cognitive behavioral therapy, intervertebral disc (IVD) degeneration, physiotherapy, physical activity, and walking were the recent hot topics and physical activity was an emerging trend in LBP-O, while surgery and IVD degeneration (also a hot topic) were emerging trends in LBP-W. This study highlights the paucity of LBP-O-related research in the past. The United States and the journal Spine stand out in LBP research. The research trend of physical activity in LBP-O is consistent with the recognized importance of physical activity for older adults in general, and for managing LBP-O in particular. Conversely, the emerging trends of surgery and intervertebral disc degeneration in LBP-W research highlight a focus on the biomedical model of LBP despite LBP being a biopsychosocial condition.

ICU Resource Limitations During Peak Seasonal Influenza: Results of a 2018 National Feasibility Study.

OBJECTIVES: Demonstrate the feasibility of weekly data collection and analysis of public health emergency (PHE) data. Assess fluctuations in, and challenges of, resource matching and potential effect on patient care for influenza in ICUs. DESIGN: Multicenter prospective noninterventional study testing effectiveness of leveraging the Discovery Critical Care Research Network Program for Resilience and Emergency Preparedness (Discovery-PREP) in performing PHE research. A 20-question internet survey was developed to prospectively assess ICU influenza-related resource stress. An informatics tool was designed to track responses; data were analyzed within 24 hours of weekly survey completion by the team biostatistician for timely reporting. PARTICIPANTS: Critical care and Emergency Medicine Discovery-PREP network investigators self-selected to participate in the voluntary query. SETTING: ICUs of 13 hospitals throughout the United States, 12 academic, and one community. INTERVENTIONS: ICU physicians were electronically surveyed weekly over 17 weeks during the influenza season (January 2018-April 2018). Responses were collected for 48 hours after each email query. MEASUREMENTS AND MAIN RESULTS: The average weekly response among the sites was 79% (range, 65-100%). Significant stress, defined as alterations in ICU staffing and/or resource allocation, occurred in up to 41% of sites during the national peak of influenza activity. These alterations included changes in staffing, not accepting external patient transfers, and canceling elective surgery. During this same period, up to 17% of the sites indicated that these changes might not have been sufficient to prevent potentially avoidable patient harm. CONCLUSIONS: This novel approach to querying ICU operational stress indicated that almost half of participating sites experienced critical care resource limitations during peak influenza season and required process and/or staffing changes to better balance resources with patient care demands. This weekly national reporting infrastructure could be adapted and expanded to better inform providers, hospital emergency management teams, and government leaders during PHEs.

Identifying biopsychosocial factors that impact decompressive laminectomy outcomes in veterans with lumbar spinal stenosis: a prospective cohort study.

ABSTRACT: One in 3 patients with lumbar spinal stenosis undergoing decompressive laminectomy (DL) to alleviate neurogenic claudication do not experience substantial improvement. This prospective cohort study conducted in 193 Veterans aimed to identify key spinal and extraspinal factors that may contribute to a favorable DL outcome. Biopsychosocial factors evaluated pre-DL and 1 year post-DL were hip osteoarthritis, imaging-rated severity of spinal stenosis, scoliosis/kyphosis, leg length discrepancy, comorbidity, fibromyalgia, depression, anxiety, pain coping, social support, pain self-efficacy, sleep, opioid and nonopioid pain medications, smoking, and other substance use. The Brigham Spinal Stenosis (BSS) questionnaire was the main outcome. Brigham Spinal Stenosis scales (symptom severity, physical function [PF], and satisfaction [SAT]) were dichotomized as SAT < 2.42, symptom severity improvement ≥ 0.46, and PF improvement ≥ 0.42, and analyzed using logistic regression. Sixty-two percent improved in 2 of 3 BSS scales (ie, success). Baseline characteristics associated with an increased odds of success were-worse BSS PF (odds ratio [OR] 1.24 [1.08-1.42]), greater self-efficacy for PF (OR 1.30 [1.08-1.58]), lower self-efficacy for pain management (OR 0.80 [0.68-0.94]), less apparent leg length discrepancy (OR 0.71 [0.56-0.91]), greater self-reported alcohol problems (OR 1.53 [1.07-2.18]), greater treatment credibility (OR 1.31 [1.07-1.59]), and moderate or severe magnetic resonance imaging-identified central canal stenosis (OR 3.52 [1.06-11.6]) moderate, OR 5.76 [1.83-18.1] severe). Using opioids was associated with lower odds of significant functional improvement (OR 0.46 [0.23-0.93]). All P < 0.05. Key modifiable factors associated with DL success-self-efficacy, apparent leg length inequality, and opioids-require further investigation and evaluation of the impact of their treatment on DL outcomes.

Do Decision Aids Benefit Patients with Chronic Musculoskeletal Pain? A Systematic Review.

OBJECTIVE: To review the effect of patient decision aids for adults making treatment decisions regarding the management of chronic musculoskeletal pain. METHODS: We performed a systematic review of randomized controlled trials of adults using patient decision aids to make treatment decisions for chronic musculoskeletal pain in the outpatient setting. RESULTS: Of 477 records screened, 17 met the inclusion criteria. Chronic musculoskeletal pain conditions included osteoarthritis of the hip, knee, or trapeziometacarpal joint and back pain. Thirteen studies evaluated the use of a decision aid for deciding between surgical and nonsurgical management. The remaining four studies evaluated decision aids for nonsurgical treatment options. Outcomes included decision quality, pain, function, and surgery utilization. The effects of decision aids on decision-making outcomes were mixed. Comparing decision aids with usual care, all five studies that examined knowledge scores found improvement in patient knowledge. None of the four studies that evaluated satisfaction with the decision-making process found a difference with use of a decision aid. There was limited and inconsistent data on other decision-related outcomes. Of the eight studies that evaluated surgery utilization, seven found no difference in surgery rates with use of a decision aid. Five studies made comparisons between different types of decision aids, and there was no clearly superior format. CONCLUSIONS: Decision aids may improve patients' knowledge about treatment options for chronic musculoskeletal pain but largely did not impact other outcomes. Future efforts should focus on improving the effectiveness of decision aids and incorporating nonpharmacologic and nonsurgical management options.

Aging Back Clinics-a Geriatric Syndrome Approach to Treating Chronic Low Back Pain in Older Adults: Results of a Preliminary Randomized Controlled Trial.

OBJECTIVE: Treating chronic low back pain (CLBP) with spine-focused interventions is common, potentially dangerous, and often ineffective. This preliminary trial tests the feasibility and efficacy of caring for CLBP in older adults as a geriatric syndrome in Aging Back Clinics (ABC). DESIGN: Randomized controlled trial. SETTING: Outpatient clinics of two VA Medical Centers. SUBJECTS: Fifty-five English-speaking veterans aged 60-89 with CLBP and no red flags for serious underlying illness, prior back surgery, dementia, impaired communication, or uncontrolled psychiatric illness. METHODS: Participants were randomized to ABC care or usual care (UC) and followed for six months. ABC care included 1) a structured history and physical examination to identify pain contributors, 2) structured participant education, 3) collaborative decision-making, and 4) care guided by condition-specific algorithms. Primary outcomes were low back pain severity (0-10 current and seven-day average/worst pain) and pain-related disability (Roland Morris). Secondary outcomes included the SF-12 and health care utilization. RESULTS: ABC participants experienced significantly greater reduction in seven-day average (-1.22 points, P = 0.023) and worst pain (-1.70 points, P = 0.003) and SF-12 interference with social activities (50.0 vs 11.5%, P = 0.0030) at six months. ABC participants were less likely to take muscle relaxants (16.7 vs 42.3%, P = 0.0481). Descriptively, UC participants were more likely to experience pain-related emergency room visits (45.8% vs 30.8%) and to be exposed to non-COX2 nonsteroidal anti-inflammatory drugs (73.1% vs 54.2%). CONCLUSIONS: These preliminary data suggest that ABC care for older veterans with CLBP is feasible and may reduce pain and exposure to other potential morbidity.

Biopsychosocial Profiles and Functional Correlates in Older Adults with Chronic Low Back Pain: A Preliminary Study.

OBJECTIVE: To describe key peripheral and central nervous system (CNS) conditions in a group of older adults with chronic low back pain (CLBP) and their association with pain severity and self-reported and performance-based physical function. DESIGN: Cross-sectional. SETTING: Outpatient VA clinics. SUBJECTS: Forty-seven community-dwelling veterans with CLBP (age 68.0 ± 6.5 years, range = 60-88 years, 12.8% female, 66% white) participated. METHODS: Data were collected on peripheral pain generators-body mass index, American College of Rheumatology hip osteoarthritis criteria, neurogenic claudication (i.e., spinal stenosis), sacroiliac joint (SIJ) pain, myofascial pain, leg length discrepancy (LLD), and iliotibial band pain; and CNS pain generators-anxiety (GAD-7), depression (PHQ-9), insomnia (Insomnia Severity Index), maladaptive coping (Fear Avoidance Beliefs Questionnaire, Cognitive Strategies Questionnaire), and fibromyalgia (fibromyalgia survey). Outcomes were pain severity (0 to 10 scale, seven-day average and worst), self-reported pain interference (Roland Morris [RM] questionnaire), and gait speed. RESULTS: Approximately 96% had at least one peripheral CLBP contributor, 83% had at least one CNS contributor, and 80.9% had both peripheral and CNS contributors. Of the peripheral conditions, only SIJ pain and LLD were associated with outcomes. All of the CNS conditions and SIJ pain were related to RM score. Only depression/anxiety and LLD were associated with gait speed. CONCLUSIONS: In this sample of older veterans, CLBP was a multifaceted condition. Both CNS and peripheral conditions were associated with self-reported and performance-based function. Additional investigation is required to determine the impact of treating these conditions on patient outcomes and health care utilization.

Managing Acute Pain and Opioid Risks Following Wisdom Teeth Extraction: An Illustrative Case.

Introduction: The opioid epidemic has awakened educators to the insufficiency of training in the areas of pain management and substance use disorders within the curricula of health sciences schools. The University of Pittsburgh Center of Excellence in Pain Education created an online educational module focusing on factors contributing to the opioid epidemic and the role of robust interprofessional communication in avoiding common practitioner errors. Methods: The 1-hour module created by an interprofessional team comprised a pretest, video presentation featuring case vignettes, posttest, and learner satisfaction survey. The content of the module focused on four core concepts: (1) managing acute perioperative pain, (2) maximizing opioid safety, and (3) identifying and (4) managing suspected opioid abuse and diversion. Results: Data were obtained from 250 dental, pharmacy, and nursing students from the University of Pittsburgh who completed the module as part of their respective profession-specific curricula. Results collapsed across the three school-specific implementations indicated an average increase in knowledge test scores from pre- to posttest (Z = -8.82, p < .001). In addition, the learner satisfaction data revealed an overall positive response to the module, with students commenting that they enjoyed the module and felt it provided them with a valuable learning experience. Discussion: Learner outcomes and feedback suggest that our interprofessional team was successful in creating an effective learning module applicable to several health care professions, namely, pharmacy, dentistry, and nursing. Future studies might address the application of the knowledge gained to actual patient care.

Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women.

To prevent the global health burdens of human immunodeficiency virus [HIV] and unintended/mistimed pregnancies, we developed an intravaginal ring [IVR] that delivers tenofovir [TFV] at ~10mg/day alone or with levonorgestrel [LNG] at ~20µg/day for 90 days. We present safety, pharmacokinetics, pharmacodynamics, acceptability and drug release data in healthy women. CONRAD A13-128 was a randomized, placebo controlled phase I study. We screened 86 women; 51 were randomized to TFV, TFV/LNG or placebo IVR [2:2:1] and 50 completed all visits, using the IVR for approximately 15 days. We assessed safety by adverse events, colposcopy, vaginal microbiota, epithelial integrity, mucosal histology and immune cell numbers and phenotype, cervicovaginal [CV] cytokines and antimicrobial proteins and changes in systemic laboratory measurements, and LNG and TFV pharmacokinetics in multiple compartments. TFV pharmacodynamic activity was measured by evaluating CV fluid [CVF] and tissue for antiviral activity using in vitro models. LNG pharmacodynamic assessments were timed based on peak urinary luteinizing hormone levels. All IVRs were safe with no significant colposcopic, mucosal, immune and microbiota changes and were acceptable. Among TFV containing IVR users, median and mean CV aspirate TFV concentrations remained above 100,000 ng/mL 4 hours post IVR insertion and mean TFV-diphosphate [DP] concentrations in vaginal tissue remained above 1,000 fmol/mg even 3 days post IVR removal. CVF of women using TFV-containing IVRs completely inhibited [94-100%] HIV infection in vitro. TFV/LNG IVR users had mean serum LNG concentrations exceeding 300 pg/mL within 1 hour, remaining high throughout IVR use. All LNG IVR users had a cervical mucus Insler score <10 and the majority [95%] were anovulatory or had abnormal cervical mucus sperm penetration. Estimated in vivo TFV and LNG release rates were within expected ranges. All IVRs were safe with the active ones delivering sustained high concentrations of TFV locally. LNG caused changes in cervical mucus, sperm penetration, and ovulation compatible with contraceptive efficacy. The TFV and TFV/LNG rings are ready for expanded 90 day clinical testing. Trial registration ClinicalTrials.gov #NCT02235662.

An E-learning Module on Chronic Low Back Pain in Older Adults: Effect on Medical Resident Attitudes, Confidence, Knowledge, and Clinical Skills.

Objective: To determine 1) the feasibility of implementing an e-learning module on chronic low back pain (CLBP) in an older adult into an existing internal medicine residency curriculum and 2) the impact of this module on resident attitudes, confidence, knowledge, and clinical skills relating to CLBP. Methods: Participants were assigned to complete either the online module (N = 73) or the Yale Office-based curriculum on CLBP (N = 70). Attitudes, confidence, and knowledge were evaluated pre- and postintervention via survey. A retrospective blinded chart review of resident clinic encounters was conducted, wherein diagnosis codes and physical exam documentation were rated as basic or advanced. Results: There was no improvement in overall knowledge scores in either group (60% average on both metrics). There were tendencies for greater improvements in the intervention group compared with controls for confidence in managing fibromyalgia (2.4 to 2.9 vs 2.5 to 2.5, P = 0.06) and leg length discrepancy (1.8 to 2.5 vs 1.5 to 1.9, P = 0.05). Those exposed to the online module also showed an increase in the percentage of physical exam documentation rated as advanced following the intervention (13% to 32%, P = 0.006), whereas the control group showed no change (14% to 12%, P = 0.68). Conclusions: An online module on CLBP in the older adult was a feasible addition to an existing curriculum for internal medicine residents. The module positively and substantively impacted resident clinical behaviors, as evidenced by enhanced sophistication in physical exam documentation; it also was associated with improved confidence in certain aspects of chronic pain management.

Clinical and neuropsychiatric correlates of lumbar spinal surgery in older adults: results of a pilot study.

AIM: To improve selection of older lumbar surgical candidates, we surveyed correlates of functioning and satisfaction with surgery. MATERIALS & METHODS: Prospective sample at lumbar spine surgery clinic. Patients (n = 48) were evaluated before surgery and after 3 months. Dependent variables were functioning and surgical satisfaction. RESULTS: Baseline variables associated with disability at 3 months included cognitive status and widespread pain. There was clinically significant improvement with moderate effects sizes for anxiety and depression at follow-up. Patients with at least a 30% improvement in disability had better physical health-related quality of life and were less likely to report widespread pain before surgery. CONCLUSION: Although preliminary, two novel potential predictors of lumbar surgery outcome include diminished cognitive functioning and widespread pain. Further study of these variables on post-surgical functioning and satisfaction may improve patient selection.

Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment. Part VI: Lumbar Spinal Stenosis.

OBJECTIVE: . To present the sixth in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. This article focuses on the evaluation and management of lumbar spinal stenosis (LSS), the most common condition for which older adults undergo spinal surgery. METHODS: . The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a five-member content expert panel and a nine-member primary care panel were involved in the iterative development of these materials. The illustrative clinical case was taken from the clinical practice of a contributor's colleague (SR). RESULTS: . We present an algorithm and supportive materials to help guide the care of older adults with LSS, a condition that occurs not uncommonly in those with CLBP. The case illustrates the importance of function-focused management and a rational approach to conservative care. CONCLUSIONS: . Lumbar spinal stenosis exists not uncommonly in older adults with CLBP and management often can be accomplished without surgery. Treatment should address all conditions in addition to LSS contributing to pain and disability.

Deconstructing chronic low back pain in the older adult--Step by step evidence and expert-based recommendations for evaluation and treatment part III: Fibromyalgia syndrome.

OBJECTIVE: To present the third in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of 12 important contributors to pain and disability in older adults with CLBP. This article focuses on fibromyalgia syndrome (FMS). METHODS: A modified Delphi approach was used to create the evaluation and treatment algorithm, the table discussing the rationale behind each of the algorithm components, and the stepped-care drug recommendations. The team involved in the creation of these materials consisted of a principal investigator, a 5-member content expert panel, and a 9-member primary care panel. The evaluation and treatment recommendations were based on availability of medications and other resources within the Veterans Health Administration (VHA) facilities. However, non-VHA panelists were also involved in the development of these materials, which can be applied to both VA and civilian settings. The illustrative clinical case was taken from the clinical practice of the principal investigator. RESULTS: Following expert consultations and a review of the literature, we developed an evaluation and treatment algorithm with supporting materials to aid in the care of older adults with CLBP who have concomitant FMS. A case is presented that demonstrates the complexity of pain evaluation and management in older patients with CLBP and concomitant FMS. CONCLUSIONS: Recognition of FMS as a common contributor to CLBP in older adults and initiating treatment targeting both FMS and CLBP may lead to improved outcomes in pain and disability.

Advancing the screening of fibromyalgia in late-life depression: practical implications for psychiatric settings.

BACKGROUND: Fibromyalgia (FM) is common in older adults suffering from mood disorders. However, clinical diagnosis of FM is challenging, particularly in psychiatric settings. We examined the prevalence of FM and the sensitivity of three simple screeners for FM. METHODS: Using cross-sectional data, we evaluated three tests against the American College of Rheumatology (ACR) 1990 Criteria for the Classification of FM: a "Do you often feel like you hurt all over?" question, a pain map score, and the Pope and Hudson (PH) interview for FM. Participants were 185 community-dwelling adults ≥ 60 years old with comorbid depression and chronic low back pain evaluated at a late-life mental health clinic. RESULTS: Fifty three of 185 participants (29%) met the ACR 1990 FM criteria. Compared to those without FM, the FM group had more "yes" answers to the "hurt all over?" question and higher pain map scores. To reach a sensitivity of at least 0.90, the cut-off score for the pain map was 8. The sensitivity of the pain map, "hurt all over?" question, and PH criteria were 0.92 [95%CI 0.82-0.98], 0.91 [95%CI 0.79-0.97], and 0.94 [95%CI 0.843-0.99] respectively. CONCLUSIONS: Nearly one in three older adults suffering from depression and chronic low back pain met ACR 1990 FM criteria. Three short screening tests showed high sensitivity when compared to the ACR 1990 FM criteria. Implementation of one of the simple screeners for FM in geriatric psychiatry settings may guide the need for further diagnostic evaluation.

Goal Attainment Scaling (GAS) in geriatric primary care: a feasibility study.

OBJECTIVE: Evaluate the feasibility of generating patient-centered goals using GAS with older adults who have multiple chronic conditions, recruited through primary care. METHOD: Adults age 65+ (N=27) were recruited from a geriatric primary care center. Participants were asked to identify 2-4 activity-based goals and set attainment levels using GAS. At 8 weeks, participants were asked to rate current level of their goal performance. Physician surveys were used to evaluate if goals were realistic and feasible, and patient surveys were implemented to evaluate satisfaction. GAS T-scores were used to quantify change in goal achievement. RESULTS: Ninety-three percent (n=25) of participants were able to establish a minimum of two goals using GAS. 100% of participants were able to rate goal performance at follow-up. Physician survey results identified 100% of goals realistic and 93% achievable and 100% of participants were either neutral or satisfied with the process. Significant improvement was reported in GAS change scores (t(24)=6.54, p<0.001). CONCLUSION: Findings support the feasibility of GAS for older adults with multiple chronic conditions in geriatric primary care as a strategy to facilitate patient-centered care and suggest that the process of personalized goal-setting itself may facilitate goal attainment.

Toward early safety alert endpoints: exploring biomarkers suggestive of microbicide failure.

Several microbicides, including nonoxynol-9 (N-9) and cellulose sulfate (CS), looked promising during early trials but failed in efficacy trials. We aimed to identify Phase I mucosal safety endpoints that might explain that failure. In a blinded, randomized, parallel trial, 60 healthy premenopausal sexually abstinent women applied Universal HEC placebo, 6% CS or 4% N-9 gel twice daily for 13½ days. Endpoints included immune biomarkers in cervicovaginal lavage (CVL) and endocervical cytobrushes, inflammatory infiltrates in vaginal biopsies, epithelial integrity by naked eye, colposcopy, and histology, CVL anti-HIV activity, vaginal microflora, pH, and adverse events. Twenty women enrolled per group. Soluble/cellular markers were similar with CS and placebo, except secretory leukocyte protease inhibitor (SLPI) levels decreased in CVL, and CD3(+) and CD45(+) cells increased in biopsies after CS use. Increases in interleukin (IL)-8, IL-1, IL-1RA, and myeloperoxidase (MPO) and decreases in SLPI were significant with N-9. CVL anti-HIV activity was significantly higher during CS use compared to N-9 or placebo. CS users tended to have a higher prevalence of intermediate Nugent score, Escherichia coli, and Enterococcus and fewer gram-negative rods. Most Nugent scores diagnostic for bacterial vaginosis were in N-9 users. All cases of histological inflammation or deep epithelial disruption occurred in N-9 users. While the surfactant N-9 showed obvious biochemical and histological signs of inflammation, more subtle changes, including depression of SLPI, tissue influx of CD45(+) and CD3(+) cells, and subclinical microflora shifts were associated with CS use and may help to explain the clinical failure of nonsurfactant microbicides.

Colposcopy: still useful in microbicide safety trials?

BACKGROUND: Colposcopy is used to evaluate vaginal microbicides, but its link to risk of HIV is unknown. This reanalysis of 9 safety studies determined the impact of omitting colposcopy on the number of findings detected and assessed whether colposcopy was useful in identifying nonoxynol-9 (N-9) as an unsafe product in one study. METHODS: Product-related findings seen with naked eye and colposcopy or by colposcopy alone were evaluated. Using data from one study, the ratio of findings in N-9 users to those in hydroxyethylcellulose (HEC) users was compared for findings seen by naked eye and colposcopy versus findings detected only by colposcopy. RESULTS: Of the 403 finding observations in the 9 studies, 173 (43%) would have been missed without colposcopy. Data from the N-9/HEC study showed that without colposcopy, there would have been 7 times as many observations in the N-9 group as in the HEC group (63 vs. 9). With colposcopy, the N-9/HEC ratio was 13:9 or 1.4. Considering epithelial integrity, finding type, and size showed similar patterns, except that among the smallest findings (<5 mm), the N-9/HEC ratio was 1.2 by naked eye and nearly the same at 1.4 by colposcopy. CONCLUSION: Colposcopy was not helpful in identifying an unsafe product: the conclusions reached using naked eye examination alone were more alarming regarding the safety of N-9 than reached by including colposcopy. Recommendations include: (1) naked eye examinations should be continued in microbicide studies; (2) colposcopy may be considered for early studies, such as first-in-human studies, but has no place in large studies; and (3) colposcopy should be replaced as soon as possible with a more objective validated biomarker of HIV risk.

Baseline variation and associations between subject characteristics and five cytokine biomarkers of vaginal safety among healthy non-pregnant women in microbicide trials.

Interleukins (IL)-8, IL-1α, IL-1ß, and IL-1 receptor antagonist (IL-1RA) have emerged as indicators of vaginal inflammation and HIV-1 transmission risk. We provide values and factors of normal variation of these immune mediators in premenopausal women to allow their wider clinical application as biomarkers of vaginal health. Cross-sectional analyzes (Kruskal-Wallis and Wilcoxon exact tests) of cytokine concentrations in relation to sociodemographic variables and Nugent score were performed on baseline (prior to product) cervicovaginal lavage from two Phase I randomized microbicide trials. All women in the analysis had regular menstrual cycles, 72 h abstinence, normal blood and Pap tests, and absence of genitourinary infections, study-relevant allergies, antibiotics use and history of substance abuse. Cytokine norms were defined as the values among those with Nugent score <4. Among women with normal Nugent score (n=92), IL-8 and IL-1ß were lowest in those using abstinence as compared to hormonal contraceptives or male/female sterilization as their primary method for birth control. No difference was found by age, prior pregnancy, or education, and also by race after controlling for contraceptive method. Women with abnormal (>7) and borderline (4-6) Nugent scores had elevated IL-1α and/or IL-1ß although their IL-1RA-to-IL(α+ß) ratio remained within the normal range due to higher IL-1RA. Women with borderline Nugent scores had IL-8 levels above the normal range. IL-8 and the IL-1RA-to-IL-1 ratio can be used as independent biomarkers of vaginal immune balance. More studies must determine the role of sexual activity, contraceptive method, and borderline Nugent scores, which normally are not exclusion criteria for enrollment in microbicide trials but may affect product tolerability and HIV-1 risk due to the aberrant cytokine levels.

The impact of pain and depression on recovery after coronary artery bypass grafting.

OBJECTIVE: To describe the relationship between pain and depression on recovery after coronary artery bypass grafting (CABG). METHODS: A secondary data analysis on 453 depressed and nondepressed post-CABG patients enrolled in a randomized, controlled, effectiveness trial of telephone-delivered collaborative care for depression. Outcome measures were collected from March 2004 to September 2007 and included pain, physical function, and mood symptoms. RESULTS: Depressed patients (baseline Patient Health Questionnaire-9 score ≥10) versus those without depression reported significantly worse pain scores on the 36-Item Short Form Health Survey Bodily Pain Scale at baseline and up to 12 months post-CABG, p < .05. Among patients with depression, those who received collaborative care reported significantly better pain scores at each time point between 2 and 12 months post-CABG versus depressed patients randomized to the usual care control group, p < .05. Regardless of intervention status, depressed participants with at least moderate pain at baseline reported significantly lower functional status (measured by the Duke Activity Status Index) at 8 and 12 months versus depressed patients with none or mild pain, p < .05. Depressed patients with at least moderate pain at baseline were also significantly less likely to show improvement of depressive symptoms throughout the course of follow-up versus depressed patients with little or no pain, p < .05. These findings controlled for age, gender, education, race, comorbid conditions, and baseline pain diagnosis. CONCLUSIONS: Depression and pain seem to influence functional recovery post-CABG. The relationship between these two conditions and 12-month outcomes should be considered by clinicians when planning treatment.

Quinacrine sterilization and gynecologic cancers: a case-control study in northern Vietnam.

BACKGROUND: Over 100,000 women worldwide have been sterilized by insertion of quinacrine into the uterus to induce tubal scarring. Concern has been expressed about possible carcinogenicity, and specifically the risk of uterine cancer. METHODS: From 2001 through 2006, we conducted a population-based, case-control study of gynecologic cancers in 12 provinces in northern Vietnam, where relatively large numbers of women had received quinacrine. Cases of incident cervical, ovarian, and uterine cancer were identified at provincial hospitals or at referral hospitals in Hanoi. For each case, 3 age- and residence-matched controls were randomly selected from the population registries of the case's home community. RESULTS: The prevalence of quinacrine exposure was 1.2% among cases and 1.1% among controls. For cervical cancer, analysis of 606 cases (9 exposed) and their 1774 matched controls (18 exposed) produced an odds ratio of 1.44 (95% confidence interval = 0.59-3.48) (adjusted for several covariates including human papillomavirus risk score). For ovarian cancer, based on 262 cases (3 exposed) and 755 controls (8 exposed) and adjusted for age and number of years of ovulation, the odds ratio was 1.26 (0.21-5.45). For uterine cancer, none of the cases-including 23 cases of leiomyosarcoma-was exposed to quinacrine. The 95% confidence interval, based on 161 cases (none exposed) and 470 controls (7 exposed) and adjusted only for age, was 0-1.85. CONCLUSION: We found no evidence of a relationship between quinacrine sterilization and gynecologic cancer.

Clinical practice guideline improves the treatment of sickle cell disease vasoocclusive pain.

BACKGROUND: Pain is the most common complication of sickle cell disease requiring emergency department (ED) visits and hospitalization. A Clinical Practice Guideline (CPG) to manage acute sickle cell pain offers clinicians a standardized approach for the provision of evidence-based, cost-effective care. After CPG implementation, monitoring of pre-established indicators is a strategy to evaluate progress toward meeting the goal of providing rapid, effective pain relief for patients with acute sickle cell pain. METHODS: A retrospective chart review of patients with sickle cell disease admitted through the ED at Children's Hospital Boston with the primary diagnosis of vaso-occlusive pain was performed for a period before and after implementation of the CPG. Endpoints measured were: use of a validated pain scale, time from ED triage to first dose of analgesic, use of adequate weight-based analgesic dosing, frequency and location of PCA initiation, and time from ED triage to patient controlled analgesia (PCA) initiation. RESULTS: Two hundred sixty three sickle cell pain admissions in 93 unique subjects were analyzed, 51 pre-CPG and 212 post-CPG. Statistically significant improvements in use of pain scale, appropriate weight-based analgesic dosing, utilization of PCA, and time to initiation of PCA were observed. There was not a statistically significant improvement in the percentage of subjects who received their 1st dose of analgesic within 1 hr; however the median time to first analgesic was reduced significantly from 80 to 65 min (P = 0.003). CONCLUSIONS: Implementation of a CPG to manage acute sickle cell pain in the ED improves the ability to deliver timely, effective analgesia to this patient population. Establishing and monitoring internal benchmarks provides a means for ongoing evaluation of the pre-established goals for patient care.