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A central assumption in the design and conduct of non-inferiority trials is that the active-control therapy will have the same degree of effectiveness in the planned non-inferiority trial as in the prior placebo-controlled trials used to define the non-inferiority margin. This is referred to as the 'constancy' assumption. If the constancy assumption fails, decisions based on the chosen non-inferiority margin may be incorrect, and the study runs the risk of approving an inferior product or failing to approve a beneficial product. The constancy assumption cannot be validated in a trial without a placebo arm, and it is unlikely ever to be met completely. When there are strong, observable predictors of constancy, such as dosing and adherence to the active-control product, we can specify conditions where the constancy assumption will likely fail. We propose a method for using measurable predictors of active-control effectiveness to specify non-inferiority margins targeted to the planned study population characteristics. We describe a pre-specified method, using baseline characteristics or post-baseline predictors in the active-control arm, to adapt the non-inferiority margin at the end of the study if constancy is violated. Adaptive margins can help adjust for constancy violations that will inevitably occur in real clinical trials, while maintaining pre-specified levels of Type I error and power. [ABSTRACT FROM AUTHOR]

Background: Persons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, “whole-person” strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit (“mobile unit”) with peer navigation compared to peer navigation alone to access these services at brick and mortar locations. Methods: HPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of “one-stop” integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization. Discussion: This trial responds to a need for evidence on using a “whole-person” strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care. Trial registration: ClinicalTrials.gov . Registered on 18 March 2021. [ABSTRACT FROM AUTHOR]

The World Health Organization has issued an early release revision to its antiretroviral guidelines in which PrEP (pre-exposure prophylaxis in the form of daily oral, fixed dose combination tenofovir disoproxil fumarate/emtricitabine) is recommended as a prevention option to all people at substantial risk of acquiring HIV. However, lack of effectiveness in 2 major women-only PrEP trials, VOICE and FEM-PrEP, continues to be a cause for concern about achieving effectiveness for women in Southern Africa. We conducted a series of meta-analyses of oral effectiveness of tenofovir disoproxil fumarate/emtricitabine in women including all 5 randomized placebo-controlled trials that included women. An adherence-based meta-analysis model showed that with high levels of adherence (75%), oral PrEP is estimated to be effective (relative risk = 0.39, 95% confidence interval: 0.25 to 0.60). Provided that these results apply to women in Southern Africa, future prevention trial designs in that region should account for potentially reduced HIV incidence when PrEP is available. [ABSTRACT FROM AUTHOR]

Background People who inject drugs (PWID) living with HIV experience inadequate access to antiretroviral treatment (ART) and medication for opioid use disorders (MOUD). HPTN 074 showed that an integrated intervention increased ART use and viral suppression over 52 weeks. To examine durability of ART, MOUD, and HIV viral suppression, participants could re-enroll for an extended follow-up period, during which standard-of-care (SOC) participants in need of support were offered the intervention. Methods Participants were recruited from Ukraine, Indonesia and Vietnam and randomly allocated 3:1 to SOC or intervention. Eligibility criteria included: HIV-positive; active injection drug use; 18-60 years of age; ≥1 HIV-uninfected injection partner; and viral load ≥1,000 copies/mL. Re-enrollment was offered to all available intervention and SOC arm participants, and SOC participants in need of support (off-ART or off-MOUD) were offered the intervention. Results The intervention continuation group re-enrolled 89 participants, and from week 52 to 104, viral suppression (<40 copies/mL) declined from 41% to 29% (estimated 9.4% decrease per year, 95% CI -17.0%; -1.8%). The in need of support group re-enrolled 94 participants and had increased ART (re-enrollment: 55%, week 26: 69%) and MOUD (re-enrollment: 16%, week 26: 25%) use, and viral suppression (re-enrollment: 40%, week 26: 49%). Conclusions Viral suppression declined in year 2 for those who initially received the HPTN 074 intervention and improved maintenance support is warranted. Viral suppression and MOUD increased among in need participants who received intervention during the study extension. Continued efforts are needed for widespread implementation of this scalable, integrated intervention. [ABSTRACT FROM AUTHOR]

Introduction: Long-acting injectable cabotegravir (CAB-LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) in the HPTN 083/084 trials. We compared the potential impact of expanding PrEP coverage by offering CAB-LA to men who have sex with men (MSM) in Atlanta (US), Montreal (Canada) and the Netherlands, settings with different HIV epidemics. Methods: Three risk-stratified HIV transmission models were independently parameterized and calibrated to local data. In Atlanta, Montreal and the Netherlands, the models, respectively, estimated mean TDF/FTC coverage starting at 29%, 7% and 4% in 2022, and projected HIV incidence per 100 person-years (PY), respectively, decreasing from 2.06 to 1.62, 0.08 to 0.03 and 0.07 to 0.001 by 2042. Expansion of PrEP coverage was simulated by recruiting new CAB-LA users and by switching different proportions of TDF/FTC users to CAB-LA. Population effectiveness and efficiency of PrEP expansions were evaluated over 20 years in comparison to baseline scenarios with TDF/FTC only. Results: Increasing PrEP coverage by 11 percentage points (pp) from 29% to 40% by 2032 was expected to avert a median 36% of new HIV acquisitions in Atlanta. Substantially larger increases (by 33 or 26 pp) in PrEP coverage (to 40% or 30%) were needed to achieve comparable reductions in Montreal and the Netherlands, respectively. A median 17 additional PYs on PrEP were needed to prevent one acquisition in Atlanta with 40% PrEP coverage, compared to 1000+ in Montreal and 4000+ in the Netherlands. Reaching 50% PrEP coverage by 2032 by recruiting CAB-LA users among PrEP-eligible MSM could avert >45% of new HIV acquisitions in all settings. Achieving targeted coverage 5 years earlier increased the impact by 5-10 pp. In the Atlanta model, PrEP expansions achieving 40% and 50% coverage reduced differences in PrEP access between PrEP-indicated White and Black MSM from 23 to 9 pp and 4 pp, respectively. Conclusions: Achieving high PrEP coverage by offering CAB-LA can impact the HIV epidemic substantially if rolled out without delays. These PrEP expansions may be efficient in settings with high HIV incidence (like Atlanta) but not in settings with low HIV incidence (like Montreal and the Netherlands). [ABSTRACT FROM AUTHOR]

Introduction: Long‐acting injectable cabotegravir (CAB‐LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre‐exposure prophylaxis (PrEP) in the HPTN 083/084 trials. We compared the potential impact of expanding PrEP coverage by offering CAB‐LA to men who have sex with men (MSM) in Atlanta (US), Montreal (Canada) and the Netherlands, settings with different HIV epidemics. Methods: Three risk‐stratified HIV transmission models were independently parameterized and calibrated to local data. In Atlanta, Montreal and the Netherlands, the models, respectively, estimated mean TDF/FTC coverage starting at 29%, 7% and 4% in 2022, and projected HIV incidence per 100 person‐years (PY), respectively, decreasing from 2.06 to 1.62, 0.08 to 0.03 and 0.07 to 0.001 by 2042. Expansion of PrEP coverage was simulated by recruiting new CAB‐LA users and by switching different proportions of TDF/FTC users to CAB‐LA. Population effectiveness and efficiency of PrEP expansions were evaluated over 20 years in comparison to baseline scenarios with TDF/FTC only. Results: Increasing PrEP coverage by 11 percentage points (pp) from 29% to 40% by 2032 was expected to avert a median 36% of new HIV acquisitions in Atlanta. Substantially larger increases (by 33 or 26 pp) in PrEP coverage (to 40% or 30%) were needed to achieve comparable reductions in Montreal and the Netherlands, respectively. A median 17 additional PYs on PrEP were needed to prevent one acquisition in Atlanta with 40% PrEP coverage, compared to 1000+ in Montreal and 4000+ in the Netherlands. Reaching 50% PrEP coverage by 2032 by recruiting CAB‐LA users among PrEP‐eligible MSM could avert >45% of new HIV acquisitions in all settings. Achieving targeted coverage 5 years earlier increased the impact by 5–10 pp. In the Atlanta model, PrEP expansions achieving 40% and 50% coverage reduced differences in PrEP access between PrEP‐indicated White and Black MSM from 23 to 9 pp and 4 pp, respectively. Conclusions: Achieving high PrEP coverage by offering CAB‐LA can impact the HIV epidemic substantially if rolled out without delays. These PrEP expansions may be efficient in settings with high HIV incidence (like Atlanta) but not in settings with low HIV incidence (like Montreal and the Netherlands). [ABSTRACT FROM AUTHOR]

Introduction: Multiple antiretroviral agents have demonstrated efficacy for human immunodeficiency virus (HIV) pre‐exposure prophylaxis (PrEP). As a result, clinical trials of novel agents have transitioned from placebo‐ to active‐controlled designs; however, active‐controlled trials do not provide an estimate of efficacy versus no use of PrEP. Counterfactual placebo comparisons using other data sources could be employed to provide this information. Methods: We compared the active‐controlled study (HPTN 084) of injectable cabotegravir (CAB‐LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) among women from seven countries in Africa to three external, contemporaneous randomized HIV prevention trials from which we constructed counterfactual placebo estimates. We used direct standardization via analysis weights to achieve the same distribution of person‐years between the external study and HPTN 084, across strata predictive of HIV risk (country and selected risk covariates). We estimated prevention efficacy against a counterfactual placebo to provide information on the use of CAB‐LA and FTC/TDF compared to no intervention. We compared the counterfactual placebo findings for FTC/TDF to previous placebo‐controlled trials, adjusted for observed adherence to daily pills. Results: Distribution of age and baseline prevalence of gonorrhoea and chlamydia were similar among matched counterfactual placebo and observed HPTN 084 arms after standardization. Counterfactual estimates of CAB‐LA versus placebo in all three settings showed a consistent risk reduction of 93%–94%, with lower bounds of the confidence intervals above 72%. Observed adherence (quantifiable tenofovir in plasma) in HPTN 084 was 54%–56%, and estimated efficacy of daily oral FTC/TDF against a counterfactual placebo was consistent with a predicted risk reduction of 39%–40% for this level of daily pill use. Conclusions: Counterfactual placebo rates of HIV acquisition derived from external trial data in similar locations and time can be used to support estimates of placebo‐based efficacy of a novel HIV prevention agent. External trial data must be standardized to be representative of the clinical trial cohort testing the novel HIV prevention agent, accounting for confounders. [ABSTRACT FROM AUTHOR]

Introduction: The HIV Prevention Trials Network (HPTN) 074 study demonstrated a positive effect of an integrated systems navigation and psychosocial counseling intervention on HIV treatment initiation, viral suppression, medication assisted treatment (MAT) enrollment, and risk of death among people who inject drugs (PWID). In this sub-study, we analyzed the incidence, causes, and predictors of death among HIV-infected and uninfected participants. Methods: The HPTN 074 randomized clinical trial was conducted in Indonesia, Ukraine, and Vietnam. HIV-infected PWID with unsuppressed viral load (indexes) were recruited together with at least one of their HIV-negative injection partners. Indexes were randomized in a 1:3 ratio to the intervention or standard of care. Results: The trial enrolled 502 index and 806 partner participants. Overall, 13% (66/502) of indexes and 3% (19/806) of partners died during follow-up (crude mortality rates 10.4 [95% CI 8.1–13.3] and 2.1 [1.3–3.3], respectively). These mortality rates were for indexes nearly 30 times and for partners 6 times higher than expected in a population of the same country, age, and gender (standardized mortality ratios 30.7 [23.7–39.0] and 5.8 [3.5–9.1], respectively). HIV-related causes, including a recent CD4 < 200 cells/μL, accounted for 50% of deaths among indexes. Among partners, medical conditions were the most common cause of death (47%). In the multivariable Cox model, the mortality among indexes was associated with sex (male versus female aHR = 4.2 [1.5–17.9]), CD4 count (≥ 200 versus < 200 cells/μL aHR = 0.3 [0.2–0.5]), depression (moderate-to-severe versus no/mild aHR = 2.6 [1.2–5.0]) and study arm (intervention versus control aHR = 0.4 [0.2–0.9]). Among partners, the study arm of the index remained the only significant predictor (intervention versus control aHR = 0.2 [0.0–0.9]) while controlling for the effect of MAT (never versus ever receiving MAT aHR = 2.4 [0.9–7.4]). Conclusions: The results confirm that both HIV-infected and uninfected PWID remain at a starkly elevated risk of death compared to general population. Mortality related to HIV and other causes can be significantly reduced by scaling-up ART and MAT. Access to these life-saving treatments can be effectively improved by flexible integrated interventions, such as the one developed and tested in HPTN 074. [ABSTRACT FROM AUTHOR]

Background. Human immunodeficiency virus (HIV) testing is critical for both HIV treatment and prevention. Expanding testing in hospital settings can identify undiagnosed HIV infections. Methods. To evaluate the feasibility of universally offering HIV testing during emergency department (ED) visits and inpatient admissions, 9 hospitals in the Bronx, New York and 7 in Washington, District of Columbia (DC) undertook efforts to offer HIV testing routinely. Outcomes included the percentage of encounters with an HIV test, the change from year 1 to year 3, and the percentages of tests that were HIV-positive and new diagnoses. Results. From 1 February 2011 to 31 January 2014, HIV tests were conducted during 6.5% of 1 621 016 ED visits and 13.0% of 361 745 inpatient admissions in Bronx hospitals and 13.8% of 729 172 ED visits and 22.0% of 150 655 inpatient admissions in DC. From year 1 to year 3, testing was stable in the Bronx (ED visits: 6.6% to 6.9%; inpatient admissions: 13.0% to 13.6%), but increased in DC (ED visits: 11.9% to 15.8%; inpatient admissions: 19.0% to 23.9%). In the Bronx, 0.4% (408) of ED HIV tests were positive and 0.3% (277) were new diagnoses; 1.8% (828) of inpatient tests were positive and 0.5% (244) were new diagnoses. In DC, 0.6% (618) of ED tests were positive and 0.4% (404) were new diagnoses; 4.9% (1349) of inpatient tests were positive and 0.7% (189) were new diagnoses. Conclusions. Hospitals consistently identified previously undiagnosed HIV infections, but universal offer of HIV testing proved elusive. [ABSTRACT FROM AUTHOR]

Background: Sexual contact has been shown to be a major mode of HIV transmission among people who inject drugs (PWID). This study examined gender and racial differences among PWID' sexual risk behaviors from the perspective of sexual scripts.Methods: 696 PWID enrolled from Philadelphia on HPTN 037 were classified as engaging in high-risk sex behaviors if they reported having sex in the past 30 days and condomless sex with a non-primary partner, giving/receiving sex for money, or multiple partners. A multivariable logistic regression model was used to assess associations between demographic factors and high risk sex.Results: Findings of the multivariable regression analysis demonstrated that being White (OR = 0.52, p < 0.001) and male (OR = 0.59, p = 0.002) were protective of high risk sex, while homelessness (OR = 1.7, p = 0.005), and being single (OR = 1.83, p = 0.006) were positively associated with high risk sex. African American (AA) women were 1.7 times more likely to report high-risk sex than AA men (p = 0.002), 3.28 times more likely than White men (p < 0.001), and 1.93 times more likely than White women (p < 0.001).Conclusions: Since AA women report high-risk sex behaviors more than other demographic groups, behavioral interventions for HIV risk reduction among PWID may benefit from focusing on sex-risk reduction among AA women. [ABSTRACT FROM AUTHOR]

Transgender individuals constitute an important focus for HIV prevention, but studies in this population present some unique methodologic and operational challenges. We consider issues related to sampling, sample size, number of sites, and trial cost. We discuss relevant design issues for evaluating interventions in both HIV-negative and HIV-infected transgender populations, as well as a method for assessing the impact of an intervention on population HIV incidence. We find that HIV-endpoint studies of transgender individuals will likely require fewer participants but more sites and have higher operational costs than HIV prevention trials in other populations. Because any intervention targeted to transgender individuals will likely include antiretroviral drugs, small scale studies looking at potential interactions between antiretroviral therapy and hormone therapy are recommended. Finally, assessing the impact of an intervention targeted to transgender individuals will require better information on the contribution of such individuals to the population HIV incidence. [ABSTRACT FROM AUTHOR]

Background The HPTN 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was superior to tenofovir-disoproxil fumarate/emtricitabine for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP). Integrase strand transfer inhibitor (INSTI) resistance-associated mutations (RAMs) were detected in some participants with HIV infection. We used a low viral load INSTI genotyping assay to evaluate the timing of emergence of INSTI RAMs and assessed whether HIV screening with a sensitive RNA assay would have detected HIV infection before INSTI resistance emerged. Methods Single-genome sequencing to detect INSTI RAMs was performed for samples with viral loads <500 copies/mL from 5 participants with previously identified INSTI RAMs and 2 with no prior genotyping results. Results Major INSTI RAMs were detected in all 7 cases. HIV RNA testing identified infection before major INSTI RAMs emerged in 4 cases and before additional major INSTI RAMs accumulated in 1 case. Most INSTI RAMs were detected early when the viral load was low and CAB concentration was high. Conclusions When using CAB-LA PrEP, earlier detection of HIV infection with a sensitive RNA assay may allow for earlier treatment initiation with the potential to reduce INSTI resistance risk. Further studies are needed to evaluate the value and feasibility of HIV RNA testing with CAB-LA PrEP. [ABSTRACT FROM AUTHOR]

Background: HPTN 074 evaluated an integrated HIV treatment and prevention strategy among persons who inject drugs (PWID) in Indonesia, Ukraine and Vietnam. We previously detected multiple HIV infection in 3/7 (43%) of seroconverters with 3-8 HIV strains/person. In this report, we analyzed multiple HIV infection and HIV superinfection (SI) in the HPTN 074 cohort.Methods: We analyzed samples from 70 participants in Indonesia and Ukraine who had viral loads >400 copies/mL at enrollment and the final study visit (median follow-up 2.5 years). HIV was characterized with Sanger sequencing, next-generation sequencing, and phylogenetic analysis. Additional methods were used to characterize a rare case of triple-variant SI.Results: At enrollment, multiple infection was detected in only 3 (5.2%) of 58 participants with env sequence data. SI was detected in only one of 70 participants over 172.3 person-years of follow-up (SI incidence 0.58/100 person-years, 95% confidence intervals: 0.015, 3.2). The SI case involved acquisition of three HIV strains with rapid selection of a strain with a single pol region cluster.Conclusions: These data from a large cohort of PWID suggest that intra-host viral selection and other factors may lead to underestimation of the frequency of multiple HIV infection and SI events. [ABSTRACT FROM AUTHOR]

Abstract: Adequate central nervous system noradrenergic activity enhances cognition, but excessive noradrenergic activity may have adverse effects on cognition. Previous studies have also demonstrated that noradrenergic activity is higher in older than younger adults. We aimed to determine relationships between cerebrospinal fluid (CSF) norepinephrine (NE) concentration and cognitive performance by using data from a CSF bank that includes samples from 258 cognitively normal participants aged 21–100 years. After adjusting for age, gender, education, and ethnicity, higher CSF NE levels (units of 100 pg/mL) are associated with poorer performance on tests of attention, processing speed, and executive function (Trail Making A: regression coefficient 1.5, standard error [SE] 0.77, p = 0.046; Trail Making B: regression coefficient 5.0, SE 2.2, p = 0.024; Stroop Word-Color Interference task: regression coefficient 6.1, SE 2.0, p = 0.003). Findings are consistent with the earlier literature relating excess noradrenergic activity with cognitive impairment. [Copyright &y& Elsevier]

African-American men who have sex with men (MSM) with HIV are more likely to have unsuppressed viral load than other racial/ethnic groups. HPTN 065 Study, completed in 2015, consisted of five interconnected study components conducted at clinics in Bronx, New York and Washington, D.C. Participants completed surveys with questions related to socio-demographic factors and individual-level HIV medication adherence barriers, such as forgetting doses or fear of taking medications in front of others. Descriptive analyses and ordinal logistic regression with robust standard errors were conducted. Fifty-seven per cent of participants (N = 359) were African-American (57.1%) and roughly 40% had no more than a high school education. Mean age was 48 years. Overall, MSM with viral load suppression identified fewer individual-level barriers to adherence (p <.01) and individuals with depressive symptoms identified a greater number of barriers to adherence (p <.01). Compared to African-Americans, white MSM had a lower likelihood of identifying barriers to adherence (p <.05). Findings suggest that individual-level barriers to HIV medication adherence are common among MSM, irrespective of time since diagnosis and viral suppression. Race-specific interventions which address intersectional stigma are needed to improve health outcomes among African-American MSM, who bear much of the burden of poor HIV outcomes in the United States. [ABSTRACT FROM AUTHOR]

Background Context: Posterior lumbar interbody fusion (PLIF) is a popular method of arthrodesis for surgical treatment of instabilities and degenerative conditions of the spine. With the introduction of threaded titanium cage devices, surgeons began performing PLIF procedures using these cages as stand-alone devices. Complications have been reported, however, including pseudarthrosis with persistent pain. Outcomes after revision surgical treatment for these patients with failed PLIF are not known. Purpose: To prospectively evaluate clinical outcomes of revision fusion surgery in patients who previously underwent posterior lumbar interbody fusion with stand-alone metallic cages resulting in pseudarthrosis. Study Design/setting: Prospective case series. Methods: Nineteen patients referred to the senior author were evaluated and diagnosed with pseudoarthrosis having previously undergone a PLIF procedure with stand-alone metallic cages. History, physical exam, and imaging studies were performed preoperatively and postoperatively. All underwent revision posterolateral fusion with iliac crest graft and pedicle screw instrumentation. Patient demographics, SF-36, and Oswestry Disability Index (ODI) data were collected prior to surgery and two years postoperatively. Results: Patients undergoing revision fusion surgery were found to have had extensive facetectomies and pseudarthrosis intraoperatively. Outcomes data was collected on eighteen of nineteen patients (95%). Mean clinical follow up was 3.2 years (range 2.5-3.5 years). Seventeen patients (94%) achieved a solid fusion. Improvement was noted in seven of eight SF-36 sub-categories, but was significant only in two (Physical Function and Role Emotional). There was no significant difference in ODI scores. Conclusions: Pseudarthrosis should be considered in the differential diagnosis if severe symptoms persist in patients who undergo PLIF with stand-alone metallic cages. Successful revision fusion did not always correlate with improved clinical outcomes in these challenging patients undergoing further surgery. Performing PLIF using stand-alone metallic cages, especially after total resection of the facet joints, is not advocated unless supplemental instrumentation is utilized. [ABSTRACT FROM AUTHOR]

Objective. To investigate whether grouping of patients with back pain into similar behavioral patient profiles using SF-36 scores is predictive of outcome following 1-year treatment in a multidisciplinary spine center beginning with referral for epidural steroid injection. Design. A prospective observational study was conducted on 81 consecutive patients selected for epidural steroid injections by independent physicians following common institutional criteria. Each patient completed a baseline SF-36 questionnaire as well as a numerical response pain scale. The initial SF-36 data were used to place each patient into one of three subgroups (Highly Functional, Emotional Adapters, and Dysfunctional). Follow-up SF-36 and numerical response pain scale questionnaires were completed by the patients at 1 month and 12 months following the initial epidural steroid injection. Results. Results revealed significant improvement among all three patient subgroups following multidisciplinary treatment at both 1 month and 12 months. Few differences in outcome occurred among the subgroups. Conclusion. The SF-36-determined subgroups did not predict response to a multidisciplinary pain clinic. All three subgroups showed similar improvement following treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background data: Depression is a common co-morbidity for patients with complaints of spinal pain, yet often goes undiagnosed in clinical practice. Depressed patients who are not identified do not receive a referral or recommendation for treatments that may help ease their total illness burden. Relative to the total outcomes of spine care this may increase costs, decrease overall functional outcomes, and limit patient satisfaction. Some spine care settings track functional outcomes using a general health status survey. Although a specific and reliable survey to detect depression could be employed, an additional survey would unnecessarily increase responder and analyst burdens if the general health status survey could be used instead. Objective: To identify the Mental Component Summary (MCS) cutoff score from the Short Form 36-item Health Survey (SF-36) that best predicts a positive depression score as measured by the Center for Epidemiological Study–Depression Survey (CES-D). Study design: An analysis of the diagnostic properties of the SF-36 MCS Scale as a predictor of depressive symptoms as measured by the CES-D. Outcome measures: The SF-36 is a general health survey that contains a MCS score that represents the psychological well-being and general health perception of the respondent. This composite score is norm-based (mean=50, SD=10) with lower scores representing poorer health. The CES-D has been well-studied in patients with chronic pain complaints and was used as the gold standard for determining the MCS cutoff score. A CES-D score of 19 or greater was considered positive for depressive symptoms. Patient sample: All patients entering our facility routinely complete the SF-36. Between February 2002 and October 2002, all patients scoring 30 or less on the MCS (MCS≤30) also completed the CES-D. Patients who scored 2 standard deviations below the mean (MCS=30 or less) were considered most at risk for depression. Patients scoring above 30 on their MCS (MCS>30) were considered less likely to have depressive symptoms and were randomly chosen to complete the CES-D. There were 420 patients who completed both surveys of which there were 99 MCS≤30 patients and 321 MCS>30 patients. Methods: Receiver operating characteristic (ROC) curves were used to assess the sensitivity and specificity of the SF-36 as a screening tool for detecting depressive symptoms. Results: An MCS score of 35 has a sensitivity of 80% (76–83; 95% confidence interval), a specificity of 90% (87–93), an ROC area of 0.8517 (0.81–0.89), and correctly identified 87% of the sample. Conclusion: The SF-36 provides the benefits of a general functional health status measure and additionally appears to provide a screening tool for depressive symptoms. A cutoff score of 35 or less on the MCS scale has a high degree of sensitivity and specificity and is able to identify depressive symptoms in patients with back pain, which can help identify patients who will benefit from mental health treatments. [Copyright &y& Elsevier]

Describes the development of The Spine Center, an ambulatory clinical practice for diagnosis and treatment of spine-related problems, and summarizes the first year of operations. History of the Spine Center initiative; Mission of the center; Creation of a high performing microsystem at the center; Integration of data collection into clinical care processes.

Successful navigation of the HIV care continuum is necessary to maintain viral suppression. We explored gender-stratified correlates of being virally unsuppressed in the Prevention for Positives (P4P) component of HPTN 065. The outcome of interest was unsuppressed viral load (> 40 copies/mL) among individuals already living with HIV. Correlates included medication adherence factors, social support and stigma. Logistic regression models were stratified by gender (N = 673). Men-specific correlates of being virally unsuppressed included opposite-sex partners, older age and HIV disclosure stigma. Women-specific correlates included time since diagnosis, and personal-level barriers to medication adherence. When more individuals knew about their HIV status, women had over twice the likelihood of being virally unsuppressed; no such association was seen among men. Additionally, higher levels of social support were not associated with viral suppression among women. Interventions should consider gender-specific approaches to engaging social support in de-stigmatization of HIV and promotion of medication adherence and subsequent viral suppression. [ABSTRACT FROM AUTHOR]

Background: Persons who inject drugs (PWID) have high HIV incidence and prevalence, and may have limited access to antiretroviral therapy (ART) in some settings. We evaluated HIV drug resistance in PWID in a randomized clinical trial (HPTN 074). The study intervention included ART at any CD4 cell count with enhanced support for ART and substance use treatment. Methods: HPTN 074 enrolled HIV-infected PWID (index participants) with viral loads ≥1,000 copies/mL and their HIV-uninfected injection-network partners in Indonesia, Ukraine, and Vietnam; the study limited enrollment of people who reported being on ART. HIV drug resistance testing and antiretroviral (ARV) drug testing were performed using samples collected from index participants at study enrollment. Results: Fifty-four (12.0%) of 449 participants had HIV drug resistance; 29 (53.7%) of the 54 participants had multi-class resistance. Prevalence of resistance varied by study site and was associated with self-report of prior or current ART, detection of ARV drugs, and a history of incarceration. Resistance was detected in 10 (5.6%) of 177 newly diagnosed participants. Participants with resistance at enrollment were less likely to be virally suppressed after 52 weeks of follow-up, independent of study arm. Conclusions: In HPTN 074, many of the enrolled index participants had HIV drug resistance and more than half of those had multi-class resistance. Some newly-diagnosed participants had resistance, suggesting that they may have been infected with drug-resistant HIV strains. Behavioral and geographic factors were associated with baseline resistance. Baseline resistance was associated with reduced viral suppression during study follow-up. These findings indicate the need for enhanced HIV care in this high-risk population to achieve sustained viral suppression on ART. [ABSTRACT FROM AUTHOR]

Given ethical concerns about research involving people who inject drugs and those affected by HIV, identifying potential participation benefits is important. We evaluated participant‐reported benefits in a trial conducted in Indonesia, Ukraine, and Vietnam that assessed an intervention combining psychosocial counseling and referral for antiretroviral therapy and substance use treatment for HIV‐infected people who use drugs. Reported benefits were aggregated into three groups: clinical (antiretroviral therapy, reduced cravings, reduced drug use, lab testing, medical referral, mental health, physical health), social (employment, financial, relationships, reduced stigma), and general (gained knowledge, life improvement). Overall, 438 index participants (90.5%) and 642 injection partners (83.1%) reported at least one benefit. Significantly more index participants who received the study intervention reported at least one benefit versus those who received the standard of care. Clinical trial participation can provide broad direct and indirect benefits for stigmatized populations, which has implications for assessing the ethical appropriateness of studies with such populations. [ABSTRACT FROM AUTHOR]

Introduction: People who inject drugs (PWID) experience high HIV incidence and face significant barriers to engagement in HIV care and substance use treatment. Strategies for HIV treatment as prevention and substance use treatment present unique challenges in PWID that may vary regionally. Understanding differences in the risk structure for HIV transmission and disease progression among PWID is essential in developing and effectively targeting intervention strategies of HIV treatment as prevention. Methods: We present a baseline analysis of HIV Prevention Trials Network (HPTN) 074, a two‐arm, randomized controlled trial among PWID in Indonesia (n = 258), Ukraine (n = 457) and Vietnam (n = 439). HPTN 074 was designed to determine the feasibility, barriers and uptake of an integrated intervention combining health systems navigation and psychosocial counselling for the early engagement of antiretroviral therapy (ART) and substance use treatment for PWID living with HIV. Discordant PWID networks were enrolled, consisting of an HIV‐positive index and their HIV‐negative network injection partner(s). Among the enrolled cohort of 1154 participants (502 index participants and 652 network partners), we examine regional differences in the baseline risk structure, including sociodemographics, HIV and substance use treatment history, and injection and sexual risk behaviours. Results: The majority of participants were male (87%), with 82% of the enrolled females coming from Ukraine. The overall mean age was 34 (IQR: 30, 38). Most commonly injected substances included illegally manufactured methadone in Ukraine (84.2%), and heroin in Indonesia (81.8%) and Vietnam (99.5%). Injection network sizes varied by region: median number of people with whom participants self‐reported injecting drugs was 3 (IQR: 2, 5) in Indonesia, 5 (IQR: 3, 10) in Ukraine and 3 (IQR: 2, 4) in Vietnam. Hazardous alcohol use, assessed using the Alcohol Use Disorders Identification Test – Alcohol Consumption Questions (AUDIT‐C), was prominent in Ukraine (54.7%) and Vietnam (26.4%). Reported sexual risk behaviours in the past month, including having two or more sex partners and giving/receiving money or drugs in exchange for sex, were uncommon among all participants and regions. Conclusions: While regional differences in risk structure exist, PWID particularly in Ukraine need immediate attention for risk reduction strategies. Substantial regional differences in risk structure will require flexible, tailored treatment as prevention interventions for distinct PWID populations. [ABSTRACT FROM AUTHOR]

Background: People who inject drugs (PWID) have a high incidence of HIV, little access to antiretroviral therapy (ART) and medication-assisted treatment (MAT), and high mortality. We aimed to assess the feasibility of a future controlled trial based on the incidence of HIV, enrolment, retention, and uptake of the intervention, and the efficacy of an integrated and flexible intervention on ART use, viral suppression, and MAT use.Methods: This randomised, controlled vanguard study was run in Kyiv, Ukraine (one community site), Thai Nguyen, Vietnam (two district health centre sites), and Jakarta, Indonesia (one hospital site). PWID who were HIV infected (index participants) and non-infected injection partners were recruited as PWID network units and were eligible for screening if they were aged 18-45 years (updated to 18-60 years 8 months into study), and active injection drug users. Further eligibility criteria for index participants included a viral load of 1000 copies per mL or higher, willingness and ability to recruit at least one injection partner who would be willing to participate. Index participants were randomly assigned via a computer generated sequence accessed through a secure web portal (3:1) to standard of care or intervention, stratified by site. Masking of assignment was not possible due to the nature of intervention. The intervention comprised systems navigation, psychosocial counselling, and ART at any CD4 count. Local ART and MAT services were used. Participants were followed up for 12-24 months. The primary objective was to assess the feasibility of a future randomised controlled trial. To achieve this aim we looked at the following endpoints: HIV incidence among injection partners in the standard of care group, and enrolment and retention of HIV-infected PWID and their injection partners and the uptake of the integrated intervention. The study was also designed to assess the feasibility, barriers, and uptake of the integrated intervention. Endpoints were assessed in a modified intention-to-treat popualtion after exclusion of ineligible participants. This trial is registered on ClinicalTrials.gov, NCT02935296, and is active but not recruiting new participants.Findings: Between Feb 5, 2015, and June 3, 2016, 3343 potential index participants were screened, of whom 502 (15%) were eligible and enrolled. 1171 injection partners were referred, and 806 (69%) were eligible and enrolled. Index participants were randomly assigned to intervention (126 [25%]) and standard of care (376 [75%]) groups. At week 52, most living index participants (389 [86%] of 451) and partners (567 [80%] of 710) were retained, and self-reported ART use was higher among index participants in the intervention group than those in the standard of care group (probability ratio [PR] 1·7, 95% CI 1·4-1·9). Viral suppression was also higher in the intervention group than in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Index participants in the intervention group reported more MAT use at 52 weeks than those in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Seven incident HIV infections occurred, and all in injection partners in the standard of care group (intervention incidence 0·0 per 100 person-years, 95% CI 0·0-1·7; standard of care incidence 1·0 per 100 person-years, 95% CI 0·4-2·1; incidence rate difference -1·0 per 100 person-years, 95% CI -2·1 to 1·1). No severe adverse events due to the intervention were recorded.Interpretation: This vanguard study provides evidence that a flexible, scalable intervention increases ART and MAT use and reduces mortality among PWID. The low incidence of HIV in both groups impedes a future randomised, controlled trial, but given the strength of the effect of the intervention, its implementation among HIV-infected PWID should be considered.Funding: US National Institutes of Health. [ABSTRACT FROM AUTHOR]

Abstract: The Functional Assessment of Chronic Illness Therapy (FACIT) system provides a general, multidimensional measure of health-related quality of life (FACT-G) that can be augmented with disease or symptom-specific subscales. The 19-item palliative care subscale of the FACIT system has undergone little psychometric evaluation to date. The aim of this paper is to report the internal consistency, factor structure, and construct validity of the instrument using the palliative care subscale (FACIT-Pal). Two hundred fifty-six persons with advanced cancer in a randomized trial testing a palliative care psychoeducational intervention completed the 46-item FACIT-Pal at baseline. Internal consistency was greater than 0.74 for all subscales and the total score. Seventeen of the 19 palliative care subscale items loaded onto the four-factor solution of the established core measure (FACT-G). As hypothesized, total scores were correlated with measures of symptom intensity (r =−0.73, P <0.001) and depression (r =−0.75, P <0.001). The FACIT-Pal was able to discriminate between participants who died within three months of completing the baseline and participants who lived for at least one year after completing the baseline assessment (t =−4.05, P <0.001). The functional well-being subscale discriminated between participants who had a Karnofsky performance score of 70 and below and participants with a Karnofsky performance score of 80 and above (t =3.40, P <0.001). The findings support the internal consistency reliability and validity of the FACIT-Pal as a measure of health-related quality of life for persons with advanced cancer. [Copyright &y& Elsevier]

Study Design: Spine Patient Outcomes Research Trial observational and randomized cohort participants with a confirmed diagnosis of intervertebral disc herniation (IDH) who received either usual nonoperative care and/or standard open discectomy were followed from baseline at 6 weeks, 3, 6, 12, and 24 months at 13 spine clinics in 11 US states.Objective: To evaluate the cost-effectiveness of surgery relative to nonoperative care among patients with a confirmed diagnosis of lumbar IDH.Summary Of Background Data: The cost-effectiveness of surgery as a treatment for conditions associated with low back and leg symptoms remains poorly understood.Methods: Incremental cost-effectiveness ratio, reported as discounted cost per quality adjusted life year (QALY) gained in 2004 US dollars based on EuroQol EQ-5D health state values with US scoring, and information on resource utilization and time away from work.Results: Among 775 patients who underwent surgery and 416 who were treated nonoperatively, the mean difference in QALYs over 2 years was 0.21 (95% CI: 0.16-0.25) in favor of surgery. Surgery was more costly than nonoperative care; the mean difference in total cost was $14,137(95% CI: $11,737-16,770). The cost per QALY gained for surgery relative to nonoperative care was $69,403 (95% CI: $49,523-94,999) using general adult surgery costs and $34,355 (95% CI: $20,419-52,512) using Medicare population surgery costs.Conclusion: Surgery for IDH was moderately cost-effective when evaluated over 2 years. The estimated economic value of surgery varied considerably according to the method used for assigning surgical costs. [ABSTRACT FROM AUTHOR]

The article presents a study that evaluates the cost-effectiveness of surgical compared to nonoperative treatment for intervertebral disc herniation (IDH). It is said that there is a lack of information available to evaluate the cost-effectiveness of surgery in nonoperative care among patients with lumbar IDH. It is cited that the cost of surgery for IDH varied according to the method used.

Background: Each year, greater than a half million people die of cancer in the U.S. Despite progress in increasing access to palliative oncology services, end-of-life care still needs improvement. Measuring the quality of the end-of-life experience is difficult because of patient debility and reduced consciousness as death approaches. Family proxies have been proposed as valuable informants regarding the quality of end-of-life care. This article describes family proxy perspectives concerning care at the end of life in patients who died of advanced cancer.Methods: In the context of a novel outpatient palliative care demonstration project, 125 family proxy respondents completed a structured survey by telephone 3 months to 6 months after the patient's death from breast, lung, or gastrointestinal cancer. Four key quality of care indicators were measured: decision-making and physician communication, location of death, hospice involvement, and end-of-life symptoms.Results: Proxies reported that 78% to 81% of patients completed at least 1 form of advance directive and approximately half of them were helpful in guiding care. Communication with physicians regarding end-of-life treatment wishes occurred in 67% of cases, but only 57% of the patients actually made a plan with their physician to ensure that their wishes were followed. The majority of patients died in their location of choice, most often at home, and greater than half had hospice involvement for an average of 41.8 days before death. During the last week of life, the majority of patients experienced troublesome physical and emotional symptoms.Conclusions: Measurement of proxy perspectives is feasible as an indicator of the quality of end-of-life care, and the results of the current study provide actionable data for areas of improvement in palliative oncology care. [ABSTRACT FROM AUTHOR]

Background: Surgery for spinal stenosis is widely performed, but its effectiveness as compared with nonsurgical treatment has not been shown in controlled trials. Methods: Surgical candidates with a history of at least 12 weeks of symptoms and spinal stenosis without spondylolisthesis (as confirmed on imaging) were enrolled in either a randomized cohort or an observational cohort at 13 U.S. spine clinics. Treatment was decompressive surgery or usual nonsurgical care. The primary outcomes were measures of bodily pain and physical function on the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) and the modified Oswestry Disability Index at 6 weeks, 3 months, 6 months, and 1 and 2 years. Results: A total of 289 patients were enrolled in the randomized cohort, and 365 patients were enrolled in the observational cohort. At 2 years, 67% of patients who were randomly assigned to surgery had undergone surgery, whereas 43% of those who were randomly assigned to receive nonsurgical care had also undergone surgery. Despite the high level of nonadherence, the intention-to-treat analysis of the randomized cohort showed a significant treatment effect favoring surgery on the SF-36 scale for bodily pain, with a mean difference in change from baseline of 7.8 (95% confidence interval, 1.5 to 14.1); however, there was no significant difference in scores on physical function or on the Oswestry Disability Index. The as-treated analysis, which combined both cohorts and was adjusted for potential confounders, showed a significant advantage for surgery by 3 months for all primary outcomes; these changes remained significant at 2 years. Conclusions: In the combined as-treated analysis, patients who underwent surgery showed significantly more improvement in all primary outcomes than did patients who were treated nonsurgically. [ABSTRACT FROM AUTHOR]

Study Design: Combined analysis of 2 prospective clinical studies.Objective: To identify socioeconomic characteristics associated with workers' compensation in patients with an intervertebral disc herniation (IDH) or spinal stenosis (SpS).Summary Of Background Data: Few studies have compared socioeconomic differences between those receiving or not receiving workers' compensation with the same underlying clinical conditions.Methods: Patients were identified from the Spine Patient Outcomes Research Trial (SPORT) and the National Spine Network (NSN) practice-based outcomes study. Patients with IDH and SpS within NSN were identified satisfying SPORT eligibility criteria. Information on disability and work status at baseline evaluation was used to categorize patients into 3 groups: workers' compensation, other disability compensation, or work-eligible controls. Enrollment rates of patients with disability in a clinical efficacy trial (SPORT) and practice-based network (NSN) were compared. Independent socioeconomic predictors of baseline workers' compensation status were identified in multivariate logistic regression models controlling for clinical condition, study cohort, and initial treatment designation.Results: Among 3759 eligible patients (1480 in SPORT and 2279 in NSN), 564 (15%) were receiving workers' compensation, 317 (8%) were receiving other disability compensation, and 2878 (77%) were controls. Patients receiving workers' compensation were less common in SPORT than NSN (9.2% vs. 18.8%, P < 0.001), but patients receiving other disability compensation were similarly represented (8.9% vs. 7.7%, P = 0.19). In univariate analyses, many socioeconomic characteristics significantly differed according to baseline workers' compensation status. In multiple logistic regression analyses, gender, educational level, work characteristics, legal action, and expectations about ability to work without surgery were independently associated with receiving workers' compensation.Conclusion: Clinical trials involving conditions commonly seen in patients with workers' compensation may need special efforts to ensure adequate representation. Socioeconomic characteristics markedly differed between patients receiving and not receiving workers' compensation. Identifying the independent effects of workers' compensation on outcomes will require controlling for these baseline characteristics and other clinical features associated with disability status. [ABSTRACT FROM AUTHOR]

Background Context: Retrolisthesis is relatively rare but when present has been associated with increased back pain and impaired back function. Neither the prevalence of this condition in individuals with lumbar disc herniations nor its possible relation to preoperative back pain and dysfunction has been well studied.Purpose: The purposes of this study were as follows: (1) to determine the prevalence of retrolisthesis (alone or in combination with other degenerative conditions) in individuals with confirmed L5-S1 disc herniation who later underwent lumbar discectomy; (2) to determine if there is any association between retrolisthesis and degenerative changes within the same vertebral motion segment; and (3) to determine the relation between retrolisthesis (alone or in combination with other degenerative conditions) and preoperative low back pain, physical function, and quality of life.Study Design/setting: Cross-sectional study.Patient Sample: A total of 125 individuals were identified for incorporation into this study. All patients had confirmed L5-S1 disc herniation on magnetic resonance imaging (MRI) and later underwent L5-S1 discectomy. All patients were enrolled in the Spine Patient Outcomes Research Trial (SPORT) study; data were obtained from the multi-institutional database comprised of SPORT patients from across the United States.Outcome Measures: Retrolisthesis, degenerative change on MRI, and Modic changes.Methods: MRI scans of the lumbar spine were assessed at spinal level L5-S1 for all 125 patients. Retrolisthesis was defined as posterior subluxation of 8% or more. Disc degeneration was defined as any loss of disc signal on T2 imaging. Modic changes were graded 1 to 3 and collectively classified as vertebral endplate degenerative changes. The presence of facet arthropathy and ligamentum flavum hypertrophy was classified jointly as posterior degenerative changes.Results: The overall incidence of retrolisthesis at L5-S1 in our study was 23.2%. Retrolisthesis combined with posterior degenerative changes, degenerative disc disease, or vertebral endplate changes had incidences of 4.8%, 16%, and 4.8% respectively. The prevalence of retrolisthesis did not vary by sex, age, race, smoking status, or education level when compared with individuals with normal sagittal alignment. However, individuals with retrolisthesis were more likely to be receiving workers' compensation than those without retrolisthesis. Increased age was found to be associated with individuals having vertebral endplate degenerative changes (both alone and in conjunction with retrolisthesis) and degenerative disc disease. Individuals who had retrolisthesis with concomitant vertebral endplate degenerative changes were more often smokers and had no insurance. The presence of retrolisthesis was not associated with an increased incidence of having degenerative disc disease, posterior degenerative changes, or vertebral endplate changes. No statistical significance was found between the presence of retrolisthesis on the degree of patient preoperative low back pain and physical function. Patients with degenerative disc disease were found to have increased leg pain compared with those patients without degenerative disc changes.Conclusions: We found no significant relationship between retrolisthesis in patients with L5-S1 disc herniation and worse baseline pain or function. It is possible that the contribution of pain or dysfunction related to retrolisthesis was far overshadowed by the presence of symptoms caused by the concomitant disc herniation. It remains to be seen whether retrolisthesis will affect outcome after discectomy in these patients. [ABSTRACT FROM AUTHOR]

Background: Management of degenerative spondylolisthesis with spinal stenosis is controversial. Surgery is widely used, but its effectiveness in comparison with that of nonsurgical treatment has not been demonstrated in controlled trials. Methods: Surgical candidates from 13 centers in 11 U.S. states who had at least 12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were offered enrollment in a randomized cohort or an observational cohort. Treatment was standard decompressive laminectomy (with or without fusion) or usual nonsurgical care. The primary outcome measures were the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) bodily pain and physical function scores (100-point scales, with higher scores indicating less severe symptoms) and the modified Oswestry Disability Index (100-point scale, with lower scores indicating less severe symptoms) at 6 weeks, 3 months, 6 months, 1 year, and 2 years. Results: We enrolled 304 patients in the randomized cohort and 303 in the observational cohort. The baseline characteristics of the two cohorts were similar. The one-year crossover rates were high in the randomized cohort (approximately 40% in each direction) but moderate in the observational cohort (17% crossover to surgery and 3% crossover to nonsurgical care). The intention-to-treat analysis for the randomized cohort showed no statistically significant effects for the primary outcomes. The as-treated analysis for both cohorts combined showed a significant advantage for surgery at 3 months that increased at 1 year and diminished only slightly at 2 years. The treatment effects at 2 years were 18.1 for bodily pain (95% confidence interval [CI], 14.5 to 21.7), 18.3 for physical function (95% CI, 14.6 to 21.9), and -16.7 for the Oswestry Disability Index (95% CI, -19.5 to -13.9). There was little evidence of harm from either treatment. Conclusions: In nonrandomized as-treated comparisons with careful control for potentially confounding baseline factors, patients with degenerative spondylolisthesis and spinal stenosis treated surgically showed substantially greater improvement in pain and function during a period of 2 years than patients treated nonsurgically. (ClinicalTrials.gov number, NCT00000409.) N Engl J Med 2007;356:2257-70. [ABSTRACT FROM AUTHOR]

Context: For patients with lumbar disk herniation, the Spine Patient Outcomes Research Trial (SPORT) randomized trial intent-to-treat analysis showed small but not statistically significant differences in favor of diskectomy compared with usual care. However, the large numbers of patients who crossed over between assigned groups precluded any conclusions about the comparative effectiveness of operative therapy vs usual care.Objective: To compare the treatment effects of diskectomy and usual care.Design, Setting, and Patients: Prospective observational cohort of surgical candidates with imaging-confirmed lumbar intervertebral disk herniation who were treated at 13 spine clinics in 11 US states and who met the SPORT eligibility criteria but declined randomization between March 2000 and March 2003.Interventions: Standard open diskectomy vs usual nonoperative care.Main Outcome Measures: Changes from baseline in the Medical Outcomes Study Short-Form Health Survey (SF-36) bodily pain and physical function scales and the modified Oswestry Disability Index (American Academy of Orthopaedic Surgeons/MODEMS version).Results: Of the 743 patients enrolled in the observational cohort, 528 patients received surgery and 191 received usual nonoperative care. At 3 months, patients who chose surgery had greater improvement in the primary outcome measures of bodily pain (mean change: surgery, 40.9 vs nonoperative care, 26.0; treatment effect, 14.8; 95% confidence interval, 10.8-18.9), physical function (mean change: surgery, 40.7 vs nonoperative care, 25.3; treatment effect, 15.4; 95% CI, 11.6-19.2), and Oswestry Disability Index (mean change: surgery, -36.1 vs nonoperative care, -20.9; treatment effect, -15.2; 95% CI, -18.5. to -11.8). These differences narrowed somewhat at 2 years: bodily pain (mean change: surgery, 42.6 vs nonoperative care, 32.4; treatment effect, 10.2; 95% CI, 5.9-14.5), physical function (mean change: surgery, 43.9 vs nonoperavtive care 31.9; treatment effect, 12.0; 95% CI; 7.9-16.1), and Oswestry Disability Index (mean change: surgery -37.6 vs nonoperative care -24.2; treatment effect, -13.4; 95% CI, -17.0 to -9.7).Conclusions: Patients with persistent sciatica from lumbar disk herniation improved in both operated and usual care groups. Those who chose operative intervention reported greater improvements than patients who elected nonoperative care. However, nonrandomized comparisons of self-reported outcomes are subject to potential confounding and must be interpreted cautiously.Trial Registration: clinicaltrials.gov Identifier: NCT00000410. [ABSTRACT FROM AUTHOR]

Context: Lumbar diskectomy is the most common surgical procedure performed for back and leg symptoms in US patients, but the efficacy of the procedure relative to nonoperative care remains controversial.Objective: To assess the efficacy of surgery for lumbar intervertebral disk herniation.Design, Setting, and Patients: The Spine Patient Outcomes Research Trial, a randomized clinical trial enrolling patients between March 2000 and November 2004 from 13 multidisciplinary spine clinics in 11 US states. Patients were 501 surgical candidates (mean age, 42 years; 42% women) with imaging-confirmed lumbar intervertebral disk herniation and persistent signs and symptoms of radiculopathy for at least 6 weeks.Interventions: Standard open diskectomy vs nonoperative treatment individualized to the patient.Main Outcome Measures: Primary outcomes were changes from baseline for the Medical Outcomes Study 36-item Short-Form Health Survey bodily pain and physical function scales and the modified Oswestry Disability Index (American Academy of Orthopaedic Surgeons MODEMS version) at 6 weeks, 3 months, 6 months, and 1 and 2 years from enrollment. Secondary outcomes included sciatica severity as measured by the Sciatica Bothersomeness Index, satisfaction with symptoms, self-reported improvement, and employment status.Results: Adherence to assigned treatment was limited: 50% of patients assigned to surgery received surgery within 3 months of enrollment, while 30% of those assigned to nonoperative treatment received surgery in the same period. Intent-to-treat analyses demonstrated substantial improvements for all primary and secondary outcomes in both treatment groups. Between-group differences in improvements were consistently in favor of surgery for all periods but were small and not statistically significant for the primary outcomes.Conclusions: Patients in both the surgery and the nonoperative treatment groups improved substantially over a 2-year period. Because of the large numbers of patients who crossed over in both directions, conclusions about the superiority or equivalence of the treatments are not warranted based on the intent-to-treat analysis.Trial Registration: clinicaltrials.gov Identifier: NCT00000410. [ABSTRACT FROM AUTHOR]

The article reports on the results of the Spine Patient Outcomes Research Trial intervertebral disk herniation observation cohort, a non-randomized clinical trial in which patients were able to choose whether to receive a surgical or nonsurgical treatment for lumbar disk herniation. Patients that received standard open diskectomy reported greater relief in pain than patients who chose nonoperative treatments, which included education and counseling, non-steroidal anti-inflammatory drugs, narcotic analgesic agents, physical therapy, and epidural injections.

The article presents a randomized controlled trial from the Spine Patient Outcomes Research Trial that compares the outcomes in patients who received either surgical or nonoperative treatments for lumbar disk herniation. The authors found that the symptoms of patients that underwent the surgery of lumbar diskectomy and those who received nonoperative treatments for lumbar disk herniation improved in both situations. The authors were unable to conclude whether one treatment was better than the other due to overlap of patients between the control and experimental groups.

The article presents a study which is aimed at determining the effectiveness of pain management interventions suitable for primary care physicians. Patients from 14 rural primary care practices were randomized to usual-care or intervention groups. Results were assessed with the Medical Outcomes Study 36-Item Short-Form and the Functional Interference Estimate at baseline, six months and twelve months. It can be concluded that telephone-based assistance resulted in sustained benefit in pain and psychosocial problems.

Study Design: Prospective observational cohorts.Objective: To describe sociodemographic and clinical features, and nonoperative (medical) resource utilization before enrollment, in patients who are candidates for surgical intervention for intervertebral disc herniation (IDH), spinal stenosis (SpS), and degenerative spondylolisthesis (DS) according to SPORT criteria.Summary Of Background Data: Intervertebral disc herniation, spinal stenosis, and degenerative spondylolisthesis with stenosis are the three most common diagnoses of low back and leg symptoms for which surgery is performed. There is a paucity of descriptive literature examining large patient cohorts for the relationships among baseline characteristics and medical resource utilization with these three diagnoses.Methods: The Spine Patient Outcomes Research Trial (SPORT) conducts three randomized and three observational cohort studies of surgical and nonsurgical treatments for patients with IDH, SpS, and DS. Baseline data include demographic information, prior treatments received, and functional status measured by SF-36 and the Oswestry Disability Index (ODI-AAOS/Modems version). The data presented represent all 1,411 patients (743 IDH, 365 SpS, 303 DS) enrolled in the SPORT observational cohorts. Multiple logistic regression was used to generate independent predictors of utilization adjusted for sociodemographic variables, diagnosis, and duration of symptoms.Results: The average age was 41 years for the IDH group, 64 years for the SpS group, and 66 years for the DS group. At enrollment, IDH patients presented with the most pain as reported on the SF-36 (BP 26.3 vs. 33.2 SpS and 33.8 DS) and were the most impaired (ODI 51 vs. 42.3 SpS and 41.5 DS). IDH patients used more chiropractic treatment (42% vs. 33% SpS and 26% DS), had more Emergency Department (ED) visits (21% vs. 7% SpS and 4% DS), and used more opiate analgesics (49% vs. 29% SpS and 27% DS). After adjusting for age, gender, diagnosis, education, race, duration of symptoms, and compensation, Medicaid patients used significantly more opiate analgesics (58% Medicaid vs. 41% no insurance, 42% employer, 33% Medicare, and 32% private) and had more ED visits compared with other insurance types (31% Medicaid vs. 22% no insurance, 16% employer, 3% Medicare, and 11% private).Conclusion: IDH patients appear to have differences in sociodemographics, resource utilization, and functional impairment when compared with the SpS/DS patients. In addition, the differences in resource utilization for Medicaid patients may reflect differences in access to care. The data provided from these observational cohorts will serve as an important comparison to the SPORT randomized cohorts in the future. [ABSTRACT FROM AUTHOR]

Abstract: Background context: The Short Form 36 (SF-36) health survey has been shown to be a valid instrument when used to measure the self-reported physical and mental health of patients. The impact of lumbar spinal disorders can be assessed as the difference between the SF-36 scale scores and age- and gender-specific population norms. Purpose: To establish the impact upon the self-reported health status of patients with one of four common lumbar spinal diagnoses. Study design: A cross-sectional, observational assessment of the health status of spine patients. Methods: Data from patients presenting to the participating centers of the National Spine Network with low back pain or leg pain were collected prospectively using the Health Status Questionnaire 2.0. A database search identified patients with either herniated nucleus pulposus with radicular pain (HNP), lumbar spinal stenosis without deformity (SPS), degenerative spondylolisthesis (DS), and painful disc degeneration/spondylosis (DDD). The mean SF-36 scale scores were generated for each of the diagnostic groups. The impact of these diagnoses on health status was determined as the calculated difference from the age- and gender-specific population norms for each of the eight health scale scores. These scores, usually negative in this population, represent how far below normal these patients are. The analysis was stratified according to the age of the patients (<40 years, 40–60 years, >60 years). Analysis of variance and pair-wise comparison with Bonferroni correction were used to assess the significance of differences across diagnosis and age groups. Results: Data from a total of 4,442 patients were available for this study. All four diagnostic groups had large, negative impact scores for the eight general health scales with the greatest impact upon the three scales that best measure physical health. The greatest impact on these physical health scales (physical functioning, role-physical, and bodily pain) was seen in the HNP diagnostic group. The younger age groups (<40 years and 40–60 years) had the greatest physical impairment when compared with the age- and gender-specific population norms. Analysis of variance showed a significant relationship between diagnosis and SF-36 scores, and between age groups and SF-36 scores. Conclusions: All four lumbar spine disorders have a significant negative impact on all eight of the SF-36 scales. The greatest negative impact was seen in those scales that measure physical health (role limitations due to physical symptoms [RP], physical functioning [PF], and bodily pain [BP]). The HNP diagnostic group experienced a significantly greater impact upon these three scales. This diagnostic group had the youngest patients, whose baseline physical functional status would be expected to be the most optimal. When we stratified by age in all the diagnostic groups, the greatest negative impact scores for physical health were seen in the <40 years and 40–60 years age groups. These patients were also more likely to perceive their health as poor, experience decreased energy, and have more social impairment when compared with their age/gender norms. [Copyright &y& Elsevier]

The Functional Interference Estimate (FIE) is a brief, 5-item self-report measure that assesses the degree to which pain interferes with daily functioning. While the FIE has demonstrated reliability and validity with a small normative sample, not much is known about its reliability and validity with a broad sample of individuals with pain. The current study presents FIE score means, variability estimates, reliability and validity data based on a large sample (n=1, 337) of primary care patients who report problematic pain. The FIE has excellent internal consistency and appears to have strong convergent validity with other well-established measures of function (e.g., SF-36 and Dartmouth COOP Charts). Because of its brevity and flexibility, the FIE may be a useful self-report measure of pain functional interference in clinical research on pain. [Copyright &y& Elsevier]

Study Design: Descriptive analysis of cross-sectional data collected prospectively in 20 National Spine Network (NSN) centers.Objectives: First, to summarize clinical and demographic characteristics of patients likely to need servicesfor psychosocial concerns. Second, to determine the rate and variability of referrals for behavioral medicine interventions (BMED) across the NSN.Summary Of Background Data: The prevalence of mental distress resulting from or coexisting with spinal pain is unclear. There is evidence that psychological treatments, particularly BMED, can aid the recovery of patients with symptoms of mental distress.Methods: From 1998 to 2001, 28,349 patients presenting to NSN centers completed the SF-36 General Health Survey. Patients were dichotomized by the mental component summary (MCS) score into two groups: 1) those scoring 35. Clinicians recorded a "treatment plan" comprised of a standard array of treatment options. For patients scoring Results: Baseline health status scores were lower across all SF-36 scales for the patients scoring an MCS Conclusion: With only 11.8% of mentally distressed NSN patients receiving a referral for any form of BMED, it appears that a large proportion of eligible patients are not receiving a potentially beneficial treatment. Wide variation across centers may indicate an inability to adequately assess mental distress via the usual clinical interview and examination for spinal conditions or a lack of consensus regarding BMED's availability and utility. [ABSTRACT FROM AUTHOR]

Purpose of study: Health status instruments have become important tools for understanding the impact of disease and the effectiveness of interventions. Two types of instruments are in current use. General-health surveys, such as the Short Form (SF)-36, attempt to measure the overall health status of patients, and may reflect multiple diseases or disabilities. Condition-specific surveys, such as the Oswestry, attempt to isolate the specific symptoms related to one condition and should not reflect the presence of unrelated comorbid conditions. The objectives of this study are to assess whether the SF-36 is more sensitive to the number of self-reported comorbidities than the Oswestry and to determine which comorbidities have the greatest impact on baseline health. Methods used: This is an observational study of 26,736 patients from the National Spine Network. Patients were grouped according to the number of self-reported comorbidities (0 to 5). Baseline SF-36 scores were computed for the Physical Component Summary (PCS), Bodily Pain (BP) and Physical Function (PF) scales. The Oswestry Disability Index (ODI, MODEMS version) was scored in reverse order (0 = severed disability, 100 = no disability) for consistency with the SF-36 scales. Analysis of variance was used to assess the difference in mean health status across comorbidity groups. Multiple linear regression was used to identify the most influential comorbidities. of findings: Baseline SF-36 and Oswestry scores were significantly lower for patients with a greater number of comorbidities. For patients with zero to five comorbidities, ODI scores ranged from 62.2 to 48.8, PCS scores from 33.3 to 26.0, PF scores from 50.4 to 29.1 and BP scores from 33.7 to 23.0 (p<.001 for all scales). Comorbidities most adversely impacting the ODI scores included depression, smoking, osteoporosis, osteoarthritis, blood disorders and headaches. Comorbidities most negatively impacting PCS scores include osteoarthritis, smoking, blood and lung disorders. For the BP and PF scales, the greatest negative impact came from depression, smoking, osteoporosis and osteoarthritis. Additional factors associated with low ODI and SF-36 scores included obesity, poor self-rated health, compensation and low education (factors significant at p<.01). Relationship between findings and existing knowledge: Contrary to current assumptions regarding condition-specific surveys, comorbidities are associated with lower ODI scores. The association between lower baseline ODI scores and a higher number of self-reported comorbidities may relate to worse underlying spine disease in patients with these comorbidities, but it also may reflect lack of true disease specificity for the ODI. Overall significance of findings: Clinicians and researchers should understand and consider the effect that comorbidities have on health-status measures. Further research may be necessary in order to develop a truly "condition-specific" instrument for spine patients. Disclosures: No disclosures. Conflict of interest: No conflicts. [ABSTRACT FROM AUTHOR]