Article

Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder occurring in 1:4000 worldwide.  Scoliosis is perhaps the most common skeletal problem in patients with NF1 with a prevalence of 1069%. There are two types: dystrophic and non dystrophic scoliosis.  Dystrophic scoliosis appears to have a poorer prognosis.  Dystrophic changes develop over time and may not necessarily appear at initial presentation.  Therefore the development and validation of a radiographic scheme to classify dystrophic scoliosis is needed to aide in distinguishing dystrophic from non dystrophic scoliosis and allow early detection and intervention and is our first objection. The second objective rests on the fact that NF1 has marked variability of clinical expression.  There is evidence that other genes may play a role in NF1 expression. Current research has identified candidate genetic SNP markers that can predict progressive and non-progressive curves in Adolescent Idiopathic Scoliosis (AIS) with a high degree of reliability.  If the same genetic markers are present in non-dystrophic scoliosis then this will allow earlier, more accurate prognostication, and perhaps improve treatment. Thus our hypothesis is that  NF1 patients with non-dystrophic or dystrophic scoliosis have the same genetic markers as patients with AIS. 

Evaluation of systematic review outputs and outcomes is necessary to ensure user needs are being met, demonstrate impact, plan future dissemination, and justify funding. While the EPC program has been in operation for some time, efforts to evaluate the use of our CERs are still being developed. One important ongoing activity is conducted by one of the AHRQ-funded EPCs, ECRI, which monitors and documents CER use as measured by citation in clinical practice guidelines. The RTI-UNC EPC conducted a special project to analyze the impact of two CERs, with emphasis on the creation of new research opportunities.  AHRQ, with assistance from a student intern, completed a Web utilization project, based upon report hits and downloads, for a sample of CERs. Other efforts have assessed utilization by third party payers. None of the use monitoring activities or projects to date has addressed an increasingly popular type of resource for clinicians, clinical point-of-care (POC) tools. 

Objective:  We conducted a systematic literature review of clinical trials to assess the comparative effectiveness of treatments for fibromyalgia in subgroups of highly affected or clinically complex adults. We focused on patient subgroups rather than overall treatment effects to complement a large systematic review being conducted on fibromyalgia treatments at McMaster University. 

Data sources:  We searched Medline®, Embase®, PsycINFO®, AMED, and the Cochrane Central Register of Controlled Trials (CENTRAL) plus reference lists of included studies and recent systematic reviews. 

Methods: Two investigators screened abstracts of identified references for eligibility (enrolled adults with fibromyalgia, examined treatment effects, had a control group, and assessed outcomes at least 3 months after treatment initiation). Full-text articles were reviewed to identify outcomes reporting for at least one adult subgroup: women, older or obese adults, individuals with coexisting mental health conditions, high severity or longer fibromyalgia duration, multiple medical comorbidities, or other chronic pain conditions. Primary outcomes included pain, symptom improvement, function, fatigue, sleep quality, participation, and health-related quality of life. We extracted data, assessed risk of bias of individual studies, and evaluated strength of evidence for each comparison and outcome. 

Results: We identified 22 randomized controlled trials (RCTs), 8 pooled analyses of patientlevel RCT data, and 4 observational studies that met inclusion criteria; 59 percent were drug trials. Adults with fibromyalgia and major depressive disorder (MDD) were studied most often; drug studies also reported outcomes by age, sex, race, and anxiety. Most drug trials examined duloxetine effects on pain and global improvement; trial duration was typically 3 months. Lowstrength evidence for duloxetine suggests that subgroups of adults with fibromyalgia and MDD do not experience differential short-term treatment effects. Other subgroup evidence is largely insufficient. For nearly all comparisons, treatment-by-subgroup interactions were not significant. Most interaction results were reported in text; only two RCTs and five pooled RCT analyses displayed data on subgroup outcomes. Losses to followup were considerable; dropout reporting was not subgroup specific. Adverse effects were reported for the MDD subgroup in one duloxetine pooled analysis; these were similar to overall adverse effects. Studies were not powered to detect subgroup effects. 

Conclusion: Despite the prevalent belief that fibromyalgia treatments may behave differently in subgroups, evidence to date is largely insufficient for fibromyalgia subgroup effects of interventions other than duloxetine in adults with concomitant MDD. Future studies should be designed to support subgroup analysis to improve clinical applicability.

Objective. We conducted a systematic review to examine the long-term consequences of discontinuing disease-modifying treatment (DMT) for multiple sclerosis (MS) by examining the long-term benefits and harms, and the reasons for discontinuing treatment. We also examined the evidence for people’s values, beliefs, and preferences regarding discontinuing DMT.   

Methods. Two investigators screened abstracts and full texts of identified references for eligibility. Eligible studies included studies of over 3 years that examined Food and Drug Administration–approved DMTs compared with placebo, other active DMT, or no DMT for adults with clinically isolated syndrome or MS in outpatient settings for patient-centered outcomes. We excluded studies of mitoxantrone, since it has a maximum lifetime dosage. Timing was relaxed for women who were considering pregnancy or already pregnant or patients discontinuing natalizumab due to risk factor changes. We extracted data, assessed risk of bias of individual studies, and evaluated strength of the body of evidence for each comparison and outcome. We also evaluated, using Technical Brief methods, studies of any design that examined individuals’ attitudes, values, and preferences for discontinuing treatments and health states, or factors and processes patients with MS and clinicians use in shared decisionmaking. 

Results. We identified 27 unique studies with discontinuation information: 16 of these contained complete information to allow full analysis of long-term benefits and harms. Evidence was insufficient for long-term benefits of DMTs for secondary progressive MS patients and most outcomes for relapsing-remitting MS (RRMS) patients. Low-strength evidence suggests higher long-term all-cause survival for treatment-naïve RRMS patients who did not delay starting interferon beta-1b by 2 years and used DMTs for a longer duration than for those who started later. Low-strength evidence suggests that interferon did not change RRMS patients’ disability progression. Limited low-strength evidence suggests that long-term harms do not differ from short-term harms. The majority of discontinuation tends to occur within 2 to 3 years. Another 25 unique studies provided intrapersonal, interpersonal, and shared decisionmaking information. No study directly asked why people may be reluctant to discontinue when treatment no longer seems effective; taken as a whole, the literature set provides some insight. The preferences literature underscores the complexity of the topic and the processes underlying decisionmaking. 

 Conclusions. MS patients and providers have little information to guide decisions to discontinue DMT.  

Objective:  To assess the efficacy and comparative effectiveness of surgical and nonsurgical treatments for fecal incontinence (FI) in adults. 

Data sources: Ovid MEDLINE®, Embase®, PEDro®, CINAHL®, AMED, and the Cochrane Central Register of Controlled Trials (CENTRAL); hand searches of systematic reviews. 

 Methods: Two investigators screened abstracts of identified references for eligibility (examined treatments in adults with FI published from 1980 to the present that had a control/comparator group; case series were included for surgical interventions). Full-text articles were reviewed to identify patient-reported outcomes (FI episodes, FI severity, quality of life, urgency, pain, other). We extracted data, assessed risk of bias of individual studies, and evaluated strength of evidence for each comparison and outcome.

 Results:  Sixty-three unique studies met inclusion criteria; an additional 53 surgical case series were examined for adverse effects. Enrolled adults were mostly female with mixed FI etiologies. Most randomized controlled trials (RCTs) were nonsurgical (n = 38); 13 examined pelvic floor muscle training (PFMT) and PFMT with biofeedback (PFMT-BF). Meta-analysis was not possible because numerous outcomes were used. Low-strength evidence suggests that dietary fiber (psyllium) decreases FI episodes (-2.5 per week) at 1 month; clonidine has no effect; and PFMT-BF with electrostimulation is no more effective than PFMT-BF for FI severity and the FI Quality of Life scale (FIQL) over 2 to 3 months. Low-strength evidence at 6 months suggests that dextranomer anal bulking injections are more effective than sham injections on the FIQL, the number of FI-free days, and the percent of adults with at least 50-percent reduction from baseline in FI episodes, but no more effective than PFMT-BF with or without electrostimulation on FI severity (PFMT-BF -5.4 vs. dextranomer -4.6 point Vaizey score improvements) and the FIQL, and no more effective than sham injection on FI severity (-2.5 vs. -1.7 point sham improvement in Cleveland Clinic FI score [CCFIS]) or FI episode frequency. Moderate-strength evidence suggests that Durasphere® (off label) bulking injections reduce FI severity up to 6 months (-4 to -5 points CCFIS), but gains diminish thereafter. Evidence was insufficient for all other surgical and nonsurgical comparisons. Surgical improvements varied. Noninvasive nonsurgical treatments had few minor adverse effects (AEs). Surgical treatments were associated with more frequent and more severe complications than nonsurgical interventions. AEs were most frequent for the artificial bowel sphincter (22–100% of adults). Surgical AEs ranged from minor to major (infection, bowel obstruction, perforation, fistula). Major surgical complications often required reoperation; fewer required permanent colostomy. Only 12 percent of RCTs were high quality.   

Conclusion: We found limited evidence to support any FI treatments beyond 3 to 6 months. Comparing the effectiveness of FI surgical and nonsurgical treatments is difficult because nonsurgical approaches generally precede surgery. Most current interventions show modest improvements in FI outcomes that meet minimal important differences (MIDs) in the short term, where MID is known. More invasive surgical procedures have substantial complications.

Objective. To summarize the effects of long-term osteoporosis drug treatment (ODT) and ODT discontinuation and holidays on fractures and harms. 

Objectives: The goals of this study were to identify self-reported differences in function, comorbidities, and medical service utilization among adults who reported using chiropractic and/or osteopathic manipulation in the 2012 National Health Interview Survey, and to compare these between older and younger adults.

Methods: We conducted a descriptive study of adults aged 18 or older who were included in the 2012 National Health Interview Survey and the Alternative Medicine Questionnaire. We included those who reported using chiropractic and/or osteopathic manipulation in the past 12 months. Responses were analyzed using SAS software. Weighted estimates were reported as percentages of chiropractic/osteopathic users overall and by age group (<65 years vs ≥65 years).

Results: Among the 8.5% of US adults who reported receiving manipulation, 97.6% saw chiropractors. Most adults were under age 65 (83.7%), female (56.6%), and white (85.1%). Except for sitting tolerance, functional limitations were significantly higher among older manipulation users compared with younger manipulation users (all P < .001). Older (vs younger) chiropractic/osteopathic users more often reported functional limitations (65.7% vs 37.2%), had difficulty walking without equipment (14.7% vs 2.8%), found it very difficult or were unable to walk one-quarter mile (15.7% vs 3.8%) or climb 10 steps (11.4% vs 2.5%), and needed help with instrumental activities of daily living (6.9% vs 2.0%). Comorbidities differed by age: cardiovascular events/conditions, cancer, diabetes, and arthritis were more common among older adults, and headaches, neck pain, and depression were more frequent in younger adults. Similar proportions of older and younger adults had emergency room visits (23.0% vs 21.7%); older adults reported more surgeries (26.1% vs 15.4%).

Conclusions: Notable differences exist in functional limitations and comorbidities between older and younger chiropractic and osteopathic manipulation users. This information could inform clinical practice, education, and policy.

Background: Low back pain (LBP) is a common disabling condition in older adults which often limits physical function and diminishes quality of life. Two clinical trials in older adults have shown spinal manipulative therapy (SMT) results in similar or small improvements relative to medical care; however, the effectiveness of adding SMT or rehabilitative exercise to home exercise is unclear. 

Methods: We conducted a randomized clinical trial assessing the comparative effectiveness of adding SMT or supervised rehabilitative exercise to home exercise in adults 65 or older with sub-acute or chronic LBP. Treatments were provided over 12-weeks and self-report outcomes were collected at 4, 12, 26, and 52 weeks. The primary outcome was pain severity. Secondary outcomes included back disability, health status, medication use, satisfaction with care, and global improvement. Linear mixed models were used to analyze outcomes. The primary analysis included longitudinal outcomes in the short (week 4–12) and long-term (week 4–52). An omnibus test assessing differences across all groups over the year was used to control for multiplicity. Secondary analyses included outcomes at each time point and responder analyses. This study was funded by the US Department of Health and Human Services, Health Resources and Services Administration. 

Results: 241 participants were randomized and 230 (95%) provided complete primary outcome data. The primary analysis showed group differences in pain over the one-year were small and not statistically significant. Pain severity was reduced by 30 to 40% after treatment in all 3 groups with the largest difference (eight percentage points) favoring SMT and home exercise over home exercise alone. Group differences at other time points ranged from 0 to 6 percentage points with no consistent pattern favoring one treatment. One-year post-treatment pain reductions diminished in all three groups. Secondary self-report outcomes followed a similar pattern with no important group differences, except satisfaction with care, where the two combination groups were consistently superior to home exercise alone. 

Conclusions: Adding spinal manipulation or supervised rehabilitative exercise to home exercise alone does not appear to improve pain or disability in the short- or long-term for older adults with chronic low back pain but did enhance satisfaction with care.

Learning frameworks define what an individual learner can do by detailing application of knowledge in various contexts—education, military, and employment, for instance—based on levels that indicate deeper and broader knowledge and application over time. They also provide access to alternative pathways for learners and workers to document and validate the skills required for credentials. This can increase the number of qualified candidates for employers and allow educational institutions to translate credentials and qualifications within a wider variety of learning pathways. Frameworks are important because multiple learning pathways would not connect without the translation tools that frameworks provide between and among postsecondary institutions, work-related learning, employer needs, military training and education, and community-based delivery options. With competencies as the currency, frameworks provide a mechanism to talk across providers and users of competencies by outlining how the various pieces fit together.

Background: Multilevel posterior spine fusion is associated with significant intraoperative blood loss. Tranexamic acid is an antifibrinolytic agent that reduces intraoperative blood loss. The goal of this study was to compare the percent of total blood volume lost during posterior spinal fusion (PSF) with or without tranexamic acid in patients with adolescent idiopathic scoliosis (AIS).

Methods: Thirty-six AIS patients underwent PSF in 2011-2014; the last half (n=18) received intraoperative tranexamic acid. We retrieved relevant demographic, hematologic, intraoperative and outcomes information from medical records. The primary outcome was the percent of total blood volume lost, calculated from estimates of intraoperative blood loss (numerator) and estimated total blood volume per patient (denominator, via Nadler’s equations). Unadjusted outcomes were compared using standard statistical tests.

Results: Tranexamic acid and no-tranexamic acid groups were similar (all p>0.05) in mean age (16.1 vs. 15.2 years), sex (89% vs. 83% female), body mass index (22.2 vs. 20.2 kg/m2), preoperative hemoglobin (13.9 vs. 13.9 g/dl), mean spinal levels fused (10.5 vs. 9.6), osteotomies (1.6 vs. 0.9) and operative duration (6.1 hours, both). The percent of total blood volume lost (TBVL) was significantly lower in the tranexamic acid-treated vs. no-tranexamic acid group (median 8.23% vs. 14.30%, p = 0.032); percent TBVL per level fused was significantly lower with tranexamic acid than without it (1.1% vs. 1.8%, p=0.048). Estimated blood loss (milliliters) was similar across groups.

Conclusions: Tranexamic acid significantly reduced the percentage of total blood volume lost versus no tranexamic acid in AIS patients who underwent PSF using a standardized blood loss measure.

Level of Evidence: 3. Institutional Review Board status: This medical record chart review (minimal risk) study was approved by the University of Minnesota Institutional Review Board.