A systematic review of outcome measures in initial rehabilitation of individuals with newly acquired spinal cord injury: providing evidence for clinical practice guidelines.

Management of Mental Health Disorders, Substance Use Disorders, and Suicide in Adults with Spinal Cord Injury: Clinical Practice Guideline for Healthcare Providers.

(Reprinted with permission from The American Journal of Psychiatry 2020; 177:868-872).

V Resumen

This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children. The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths to each recommendation, based on a systematic review of the literature and an assessment of the evidence using the GRADE process. The task force provided a summary of the relevant literature and the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. The following recommendations are intended to guide clinicians in choosing a specific treatment for central disorders of hypersomnolence in adults and children. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "conditional" recommendation (ie, "We suggest…") is one that requires that the clinician use clinical knowledge and experience and strongly consider the individual patient's values and preferences to determine the best course of action. Under each disorder, strong recommendations are listed in alphabetical order followed by the conditional recommendations in alphabetical order. The section on adult patients with hypersomnia because of medical conditions is categorized based on the clinical and pathological subtypes identified in ICSD-3. The interventions in all the recommendation statements were compared to no treatment. We recommend that clinicians use modafinil for the treatment of narcolepsy in adults. (STRONG). We recommend that clinicians use pitolisant for the treatment of narcolepsy in adults. (STRONG). We recommend that clinicians use sodium oxybate for the treatment of narcolepsy in adults. (STRONG). We recommend that clinicians use solriamfetol for the treatment of narcolepsy in adults. (STRONG). We suggest that clinicians use armodafinil for the treatment of narcolepsy in adults. (CONDITIONAL). We suggest that clinicians use dextroamphetamine for the treatment of narcolepsy in adults. (CONDITIONAL). We suggest that clinicians use methylphenidate for the treatment of narcolepsy in adults. (CONDITIONAL). We recommend that clinicians use modafinil for the treatment of idiopathic hypersomnia in adults. (STRONG). We suggest that clinicians use clarithromycin for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use methylphenidate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use pitolisant for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use sodium oxybate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use lithium for the treatment of Kleine-Levin syndrome in adults. (CONDITIONAL). We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to dementia with Lewy bodies in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL). We suggest that clinicians use sodium oxybate for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL). We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to myotonic dystrophy in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to multiple sclerosis in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of narcolepsy in pediatric patients. (CONDITIONAL). We suggest that clinicians use sodium oxybate for the treatment of narcolepsy in pediatric patients. (CONDITIONAL). Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(9):1881-1893.

OBJECTIVE: To systematically review the evidence for the efficacy of different rehabilitation strategies on functional ambulation following spinal cord injury (SCI). METHODS: A keyword literature search of original articles was used to identify published literature evaluating the effectiveness of any treatment or therapy on functional ambulation in people with SCI. The rigor and quality of each study were scored on standardized scales by two independent reviewers. RESULTS: The search yielded 160 articles, of which 119 were excluded for not meeting our inclusion criteria. The remaining 41 articles covered various strategies for improving gait: bodyweight supported treadmill training (BWSTT) (n=12), functional electrical stimulation (FES) (n=7), braces/orthoses (n=10), or a combination of these (n=12). There is strong evidence from randomized controlled trials that functional ambulation outcomes following body-weight supported treadmill training (BWSTT) are comparable to an equivalent intensity of overground gait training in sub-acute SCI. In chronic SCI, evidence from pre-test/post-test studies shows that BWSTT may be effective in improving functional ambulation. Pre-test/post-test or post-test only studies provide evidence that FES may augment functional ambulation in sub-acute/chronic SCI while braces may afford particular benefits to people with complete SCI to stand up and ambulate with assistive devices. CONCLUSIONS: Rehabilitation strategies that facilitate repeated practice of gait offer the greatest benefits to functional ambulation in sub-acute or chronic SCI. Supportive devices may augment functional ambulation particularly in people with incomplete SCI.

Many of the studies provided caveats to explain how or why the strategies did or did not demonstrate improvements. Overall, authors described complex health care requiring increasingly complex approaches to ensure evidence based guidelines were utilised in practice, including using multiple dissemination and implementation strategies. The review has provided evidence that a multi-pronged approach to dissemination and implementation of practice guidelines will assist in gaining significant improvements in change in knowledge, practice and patient outcomes.

Iterating Toward Convergence: Guideline Development and the Quality of Clinical Care

Reprint: 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Surgical Management of Ulcerative Colitis.

The American Psychiatric Association Practice Guideline for the Treatment of Patients With Eating Disorders.

BackgroundRestoring community walking remains a highly valued goal for persons recovering from traumatic incomplete spinal cord injury (SCI). Recently, studies report that brief episodes of low-oxygen breathing (acute intermittent hypoxia, AIH) may serve as an effective plasticity-inducing primer that enhances the effects of walking therapy in persons with chronic (> 1 year) SCI. More persistent walking recovery may occur following repetitive (weeks) AIH treatment involving persons with more acute SCI, but this possibility remains unknown. Here we present our clinical trial protocol, designed to examine the distinct influences of repetitive AIH, with and without walking practice, on walking recovery in persons with sub-acute SCI (< 12 months) SCI. Our overarching hypothesis is that daily exposure (10 sessions, 2 weeks) to AIH will enhance walking recovery in ambulatory and non-ambulatory persons with subacute (< 12 months) SCI, presumably by harnessing endogenous mechanisms of plasticity that occur soon after injury.MethodsTo test our hypothesis, we are conducting a randomized, placebo-controlled clinical trial on 85 study participants who we stratify into two groups according to walking ability; those unable to walk (non-ambulatory group) and those able to walk (ambulatory group). The non-ambulatory group receives either daily AIH (15, 90s episodes at 10.0% O2 with 60s intervals at 20.9% O2) or daily SHAM (15, 90s episodes at 20.9% O2 with 60s intervals at 20.9% O2) intervention. The ambulatory group receives either 60-min walking practice (WALK), daily AIH + WALK, or daily SHAM+WALK intervention. Our primary outcome measures assess overground walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up & Go Test). For safety, we also measure levels of pain, spasticity, systemic hypertension, and autonomic dysreflexia. We record outcome measures at baseline, days 5 and 10, and follow-ups at 1 week, 1 month, 6 months, and 12 months post-treatment.DiscussionThe goal of this clinical trial is to reveal the extent to which daily AIH, alone or in combination with task-specific walking practice, safely promotes persistent recovery of walking in persons with traumatic, subacute SCI. Outcomes from this study may provide new insight into ways to enhance walking recovery in persons with SCI.Trial registrationClinicalTrials.gov, NCT02632422. Registered 16 December 2015,

Current Resources for Evidence‐Based Practice January/February 2012

Overview of the Epidemiology Methods and Applications: Strengths and Limitations of Observational Study Designs

“Future randomized controlled studies are needed” is a conclusion all too familiar to readers of scientific articles. This statement, distributed liberally in the literature, has come to signify little more than an obligatory admission of a study’s deficiencies. It simultaneously seeks to absolve the authors of any fault from potentially exaggerating the importance of their statistical findings while leaving it to the reader to decide how to apply and disseminate the novel information. The statement also implies that higher quality studies could and should be devised and points to salvation by way of the randomized controlled trial (RCT), the pinnacle of evidence-based medicine.1 Despite this, historical and present-day data show that RCTs are undertaken less frequently in surgery than in other areas of medicine.2–4 This raises concerns about the quality of surgical research, but what can surgeons do about it? Surveys have demonstrated a preponderance of cohort studies and case series in surgical journals, with RCTs accounting for fewer than 10% of publications.5,6 Reasons for lack of quality surgical research have been attributed to unique methodologic, practical, and ethical considerations in evaluating surgical procedures, and surgeon reluctance and lack of experience with surgical trials.3,7,8 Although high-quality RCTs are something to strive for, it is also clear that not all problems in surgery can be evaluated in an RCT. Solomon and McLeod studied 250 research questions in gastrointestinal surgery and concluded that, under ideal conditions, only 38.8% could have been answered with an RCT.9 Rather than attempting to answer every question with an RCT, surgeons should focus on using the best research design for their clinical questions. A variety of study designs can shed important insights if they are applied to the correct problem and conducted with methodologic rigor. The idea, development, exploration, assessment, and long-term study (IDEAL) model is a five-stage framework developed to guide best research practices throughout progressive stages of surgical innovation (Table 1).10,11 Early stages focus on refining the technique and its safety profile, whereas later stages are generally amenable to higher levels of scientific inquiry. With consideration for the stage of development of the surgical technique being investigated, a simple stepwise approach can be applied using the highest feasible level of evidence when choosing a study design. In this article, we outline important concepts and discuss various study designs—RCTs, observational studies with control groups, and case series—with a focus on minimizing biases. We consider various practical and methodologic issues specific to surgical research throughout. Table 1. - IDEAL Stages of Surgical Innovationa Stage Objectives Study Methods 1. Idea Initial technical description of new surgical procedure or technology Case reports, case series 2a. Development Description of early experience with new procedure or technology, including technical modifications and short-term/safety-related outcomes Prospective case series, observational studies 2b. Exploration Larger exploratory study to better define the relevant comparator groups and outcomes, and evaluate feasibility of a future RCT Prospective observational studies, RCTsb 3. Assessment Definitive comparative evaluation against the standard of care RCTs, large prospective observational studiesc 4. Long-term study Collect data for surveillance in real-world practice, identify new complications, and revise indications as needed Registry-based prospective cohort studies or case-control studies, rare case reports aDeveloped from initial description of IDEAL framework by McCulloch P, Altman DG, Campbell WB, et al. No surgical innovation without evaluation: the IDEAL recommendations. Lancet 2009;374:1105–1112.bPerformed when feasible at this stage.cAppropriate when ethical or practical factors preclude performing an RCT. DESIGNING A SURGICAL RESEARCH STUDY A 1994 commentary entitled “The Scandal of Poor Medical Research” was a heated outcry for higher quality research to be performed for a purpose greater than expanding the researcher’s curriculum vitae.12 It pointed to a variety of factors plaguing medical research, including flawed designs, inadequate samples, inappropriate statistical analyses, and misleading interpretation of results. At the heart of the problem was the combination of the “publish or perish” research climate together with a “general failure to appreciate the basic principles underlying scientific research.” Although it is not the goal of this article to review these principles in detail, the concepts of validity, bias, and statistics warrant consideration for our subsequent discussion. Once a question and hypothesis have been established, choosing the study design is the next step. The process should consider ways to maximize validity and minimize bias. Internal validity refers to the accuracy with which the findings reflect true variation in the outcomes measured in the study sample, whereas external validity refers to the extent to which the findings are generalizable to clinical populations encountered in practice.13 The interplay between these concepts is complex. By way of selective inclusion and exclusion criteria, RCTs ensure that groups of patients compared are equivalent in almost all aspects, other than the treatment administered, in striving to achieve a high level of internal validity. This can come at the expense of external validity. For instance, surgeons in real-world practice encounter patients who would not meet the strict inclusion and exclusion criteria of such studies. Biases refer to factors outside of the surgical intervention that systematically influence the results of a study.14 They detract directly from the validity of the study and can occur during study design and preparation, data collection, analysis, and interpretation of results.13,14 Biases are categorized conceptually in terms of their overarching similarities.15 Important conceptual categories are selection biases, observation biases, and confounders (Table 2). Selection biases occur during design of a study and result in unintended differences between comparison groups. They are attributable to systematic flaws in the methodology used to select patients. For instance, in a nonrandomized study investigating a novel surgical procedure compared with nonoperative treatment, patients selected to undergo surgery would likely be healthier, more compliant, and have better access to care than patients treated nonoperatively. These baseline factors stack the odds in favor of surgical outcomes. Observation biases occur during data collection and can be attributed to flaws in the measurement tools used, effects of the study environment on patient behavior, or deferential attitudes of surgeons toward one of the groups. For example, surgeons may be more invested in obtaining favorable outcomes and minimizing complications of surgically treated patients, unintentionally providing better follow-up care. A confounder is any unaccounted for “third variable” responsible for the causal relationship observed in the study. This could be a patient factor, such as smoking, in a study comparing infection rates after different wound care regimens, or a treatment-related factor, such as asymmetry in the duration of postoperative immobilization, in a study comparing different interventions for fractures. Such factors could be more pertinent than the treatments themselves to the outcomes being investigated. Table 2. - Examples of Biases in Surgical Research Bias Description Means of Minimization Selection biases Nonrespondent bias Patients declining to participate in the study differ systematically from those who take part Optimizing communication of objectives, limiting burden of participating Referral bias Patients referred to clinician and recruited to study have more severe disease Predefined and evidence-based inclusion criteria Channeling bias Patients assigned to interventions based on prognostic factors Randomized studies with allocation concealment, stratification in nonrandomized studies Chronology bias Intervention group compared with historical cohort Using concurrent comparison groups Observation biases Recall bias Inaccurate reporting of treatment response by patients Using prospective design and objective outcome measurements Hawthorne effect Change in behavior as a result of participation in a study Randomization, blinding Performance bias Results influenced by variability in surgical technique or expertise Standardized protocols, different surgeons for different procedures, stratification by surgeon level of expertise Transfer bias Patients lost to follow-up differ from those who completed study By maintaining up-to-date contact information, limiting study burden, issuing reminders Detection bias Outcomes not measured uniformly in comparison groups Concurrent comparison groups, blinding, predefined objective outcomes Conflict of interest Competing interests or secondary gain influence outcomes Mandatory disclosure, randomized blinded designs Misuse of statistics and inappropriate interpretation of statistical findings are other common culprits of poor surgical research. The majority of these issues are attributable to unintentional oversights, but a small proportion are caused by deliberate fraud.16,17 Common statistical errors include inadequate power, selection of inappropriate statistical tests, and inappropriate subgroup analysis.18–20 Complex statistical techniques are often relied on to make up for deficiencies in the study design, such as lack of randomization. Studies also tend to focus on statistical differences without considering clinically important thresholds, leading to exaggeration of the findings. Like strategies to minimize bias, the use of statistics should be planned when designing the study, with primary and secondary outcome variables and the statistical plan specified a priori. A well-designed study can also simplify the statistical methods needed. A thorough understanding of validity, bias, and statistical methods is critical when selecting any of the specific study designs discussed below. RANDOMIZED CONTROLLED TRIALS Now suppose that you have formulated a novel and structurally sound research question and have the resources at your institution to conduct the ideal study. A logical approach would be to start atop the pyramid of evidence and determine whether an RCT could be devised before considering other study types at lower levels of evidence.21 RCTs are generally most appropriate in the exploration or assessment stage of surgical innovation, once the technical aspects and safety profile of the procedure are established. Conducting an RCT requires intensive devotion of resources and time. The Wrist and Radius Injury Surgical Trial, led by the senior author (K.C.C.) to evaluate outcomes of treatments for distal radius fractures, took 10 years to complete and required funding from two National Institutes of Health grants.22 Compared with other types of studies, the same factors that make the RCT a coveted entity can also make it unwieldy in surgical research. Ethical and Practical Considerations A variety of ethical and practical considerations pose challenges for surgical RCTs. Like other comparative studies, RCTs are designed to evaluate a null hypothesis, which requires a control group. Unlike pharmaceutical trials, a methodologically equivalent control in surgery, such as a placebo, is rarely possible. One might be tempted to consider nonoperative treatment to be analogous to the placebo. This common view has been the basis of many surgical trials but is often misguided. In reality, nonoperative treatments are highly variable and difficult to control. They can be interventions such as activity modification, immobilization, physical therapy, injections, or a combination thereof. Patients may also implement their own individualized lifestyle changes, such as specialized diets and fitness regimens. Even if the nonoperative treatment is tightly and reliably controlled, the natural history of the patient’s condition may confound outcomes. In surgical trials, the true equivalent of a placebo would be sham surgery, a notion that transgresses ethical boundaries except in the most selective circumstances.23 In most cases, the use of an RCT to evaluate a surgical procedure mandates clinical equipoise between the surgical treatment being investigated and some other treatment.8 Nevertheless, even the existence of true clinical equipoise does not guarantee the feasibility of an RCT. Randomization and allocation concealment can be difficult to execute.7,8 These attributes strip the patient and physician of the opportunity for shared decision-making. Patients may be uncomfortable with randomized treatment selection without input from the surgeon, or with the notion of being part of an experiment. Patients often arrive at the surgeon’s office with a preference for a particular treatment.24 Even when all of these factors are accounted for, patients who agree to participate in an RCT may differ from patients who do not consent, introducing selection bias.3 Ethical considerations are not limited to the patient. Surgeons conducting the study must strive to treat participants equally to avoid unduly influencing the results of the treatment groups. However, surgeons often have their own preferences for one procedure over another.25 If the same surgeon is performing multiple procedures in the study, he or she may also be more facile in one of the procedures, creating potential for performance bias. This brings forth the issue of blinding, which is generally easier to accomplish in medical trials than in surgical trials. Clearly, the surgeon performing the operation cannot be blinded, but it is also difficult to ensure that patients are blinded to the treatment that they received. Patients may become aware of the surgery that was performed based on the shape of a scar, length of time spent in the operating room, or some other discernible feature. The ethics of withholding information about the surgery from the patient and examiners at follow-up visits are controversial, particularly if difficulties with recovery or complications arise. Cost and challenges recruiting patients and ensuring they return to follow-up are other factors that can make the RCT unfeasible.26 Given some of the ethical and practical factors associated with RCTs, other study designs discussed below may be better options. Minimizing Bias in RCTs Good design is crucial for maximizing validity and minimizing bias. Alarmingly, analyses of all RCTs published in The Journal of Bone and Joint Surgery between 1998 and 2013 showed that trials evaluating surgical procedures (as opposed to nonoperative or medical interventions) and with surgeons as first authors scored significantly lower in quality.27,28 To illustrate features of a well-designed surgical RCT, consider a landmark trial investigating open reduction and internal fixation versus casting for minimally displaced scaphoid waist fractures (the Scaphoid Waist Internal Fixation for Fractures Trial).29 This study sought to answer a timely question that has been a longstanding area of clinical equipoise. Allocation concealment and randomization were used with a remote randomization service that stratified patients based on their pattern of fracture displacement, further minimizing confounders. Sample size was determined based on a priori power analysis, and statistical analyses were performed by a blinded statistician following a strict prespecified plan. Primary and secondary outcomes were stated from the outset, and potentially subjective radiologic tests were evaluated independently by two musculoskeletal radiologists and a surgeon. Instead of blinding patients and surgeons, the surgical technique and postoperative protocols were left to the discretion of the surgeons, allowing patient-centered care and accounting for differences in surgeons’ technical preference and skill. This practical approach sought to minimize bias while also maximizing external validity, which was important for a trial aiming to inform clinical practice on an international scale. Empiric data support the importance of sound study design on the results of an RCT. Colditz et al. found that the likelihood of an improved outcome from an experimental treatment increased significantly in the absence of randomization.30,31 In a study analyzing 250 controlled trials, treatment effects were increased by 41% when allocation concealment was inadequate and 30% when the extent of concealment was unclear.32 Trials that were not double-blinded yielded treatment effects 17% greater than double-blinded trials. Methodologic problems like these can lead to inaccurate interpretation of findings and distort knowledge found in the published literature. They can be avoided with use of validated quality checklists such as the Consolidated Standards of Reporting Clinical Trials guidelines when planning a study.33 Such frameworks serve as an important quality safeguard and should be familiar to surgeons undertaking RCTs. Grading systems specific to plastic surgery have also been developed.34 OBSERVATIONAL STUDIES WITH A CONTROL GROUP Many questions in surgery cannot be addressed with an RCT but are amenable to other study designs. A nonrandomized study with a control group should be considered when one of the ethical or practical factors discussed above precludes an RCT. Commonly used designs are cohort studies and case-control studies (Fig. 1).15 Although cohort studies are in a higher tier of evidence, both designs have specific indications, methodologic considerations, and biases.Fig. 1.: Observational study designs.Like RCTs, cohort studies can be highly influential in their scope. Because of fewer upfront demands on participants and less stringent inclusion criteria, these studies lend themselves to broader investigations when more knowledge is needed before performing an RCT. For instance, a prospective cohort study was devised to evaluate the effectiveness and safety of immediate implant-based breast reconstruction with or without mesh following mastectomy (Implant Breast Reconstruction Evaluation study).35 This is a current topic of interest for many plastic surgeons, with recent trends toward immediate reconstruction following mastectomy.36 Although previous RCTs evaluating immediate breast reconstruction had been performed, their validity was questioned because of performance biases and low sample size.37–39 The Implant Breast Reconstruction Evaluation study addressed this gap in knowledge with an exploratory design that included more than 2000 patients from 81 participating centers. Patients underwent different variations of breast reconstruction at the discretion of the treating surgeon, eliminating concerns for patient preference that are a major hindrance to RCTs in breast surgery.40 Multiple predefined primary outcomes were evaluated and multivariable logistic regression was used to control for confounders. In addition to eliminating practical hurdles of RCTs, advantages of cohort studies illustrated in this example include obtaining larger samples, evaluating multiple exposures and outcomes at once, and generating new hypotheses for future studies through an exploratory approach. Surgeons must also be aware of the pitfalls of nonrandomized studies. Without randomization, cohort studies have limited ability to account for confounders. A causal relationship is inferred from the chronologic sequence of exposures and outcomes, which is most convincing in prospective studies. Without blinding or allocation concealment, cohort studies are also susceptible to selection biases. Recall bias is a limitation for retrospective cohort studies because of factors such as inaccurate patient recall and reliance on information from patient charts.41 Variability in documentation practices makes the fidelity of large databases particularly concerning. In case-control studies, the inference of causation is especially problematic because comparison groups are selected based on their outcomes and analyzed retrospectively for exposures. Designing an observational study with a control group requires paying special attention to these inherent limitations and must be individualized to the research question. Exposures, outcomes, inclusion criteria, and statistical methods should all be planned in advance, even for studies meant to be “exploratory” or hypothesis-generating. Observational studies should be evaluated using standardized guidelines such as the Strengthening the Reporting of Observational Studies in Epidemiology framework.42,43 Retrospective cohort studies lend themselves to studying rare conditions and procedures, particularly with the availability of large national databases. Vast amounts of data can be extracted and analyzed rapidly. Meanwhile, case-control studies are useful for investigating factors underlying rare outcomes or complications. When using a registry or database, its purpose, completeness, and accuracy should be carefully evaluated.44 If the question would be better suited for an RCT and there are no major practical or ethical barriers, a higher level of evidence design should be pursued. CASE SERIES An appraisal of articles published in the general surgery literature in 1996 compared the preponderance of case series, 46% of all studies, to “comic opera,” pointing to a necessary shift toward higher quality research.6 A similar survey conducted 10 years later found the proportion of case series had decreased to 34%, with 51% of publications being cohort studies.5 Case series, which typically involve a retrospective account of outcomes from a single procedure, often from a single institution and surgeon, remain a common avenue for publishing novel information. The absence of a control group is their primary flaw, as a hypothesis cannot be tested.44 Retrospective case series are also culprits of publication bias, as new procedures with poor outcomes are unlikely to be published.45–47 Furthermore, failure to favorable results of new techniques are unlikely to be concerns about the validity of a case series from a single Case series are for providing for subsequent hypothesis They should be undertaken with specific such as the safety of a novel procedure or rare or complications. The IDEAL model the use of a case series to be appropriate in the or development first with a new procedure are a and are to the surgical To some of the pitfalls discussed prospective series should be performed with protocols for the new procedure and in of conducting the study. studies should also be to publication The use of retrospective series should be but at a involve patients without and a standardized reporting in the case of RCTs and observational studies, validated checklists can be used to minimize bias when reporting novel surgical interventions in a case A simple approach can be used to the best research design for a surgical question. with consideration for the IDEAL stage of the surgery being investigated, the highest level of appropriate for that stage should be evaluated for feasibility before considering designs at lower levels of the evidence RCTs the highest level of but are not suited for many questions. such as observation studies and case series, to be when practical and ethical considerations preclude the use of an RCT. of the study surgical research should quality design and minimize bias. funding from the National Institutes of from and and a research from to study outcomes. has no interest to in to the of this The authors would like to for and to the development of this They appreciate the review and from of at the of

In spinal cord injury (SCI), the primary mechanical injury is followed by secondary sequelae that develop over the subsequent months and manifests in biochemical, functional, and microstructural alterations, at the site of direct injury but also in the spinal cord tissue above and below the actual lesion site. Noninvasive magnetic resonance spectroscopy (MRS) can be used to assess biochemical modulation occurring in the secondary injury phase, in addition to and supporting conventional MRI, and might help predict and improve patient outcome. In this article, we aimed to examine the metabolic levels in the pons of subacute SCI by means of in vivo proton MRS at 3 T and explore the association to clinical scores. In this prospective study, between November 2015 and February 2018, single-voxel short-echo MRS data were acquired in healthy controls and in SCI subjects in the pons once during rehabilitation. Besides the single-point MRS examination, in addition, in participants with SCI, the clinical status (ie, motor, light touch, and pinprick scores) was assessed twice: (1) around the MRS session (approximately 10 weeks postinjury) and (2) before discharge (at approximately 9 months postinjury). The group differences were assessed with Kruskal-Wallis test, the post hoc comparison was assessed with Wilcoxon rank sum test, and the clinical correlations were conducted with Spearman rank correlation test. Bayes factor calculations completed the statistical part providing relevant evidence values. Twenty healthy controls (median age, 50 years; interquartile range, 41-55 years; 18 men) and 18 subjects with traumatic SCI (median age, 50 years; interquartile range, 32-58 years; 16 men) are included. Group comparison showed an increase of total N -acetylaspartate and combined glutamate and glutamine levels in complete SCI and a reduction of total creatine in incomplete paraplegic SCI. The proton MRS-based glutathione levels at baseline correlate to the motor score improvement during rehabilitation in incomplete subacute SCI. This exploratory study showed an association of the metabolite concentration of glutathione in the pons assessed at approximately 10 weeks after injury with the improvements of the motor score during the rehabilitation. Pontine glutathione levels in subjects with traumatic subacute incomplete SCI acquired remote from the injury site correlate to clinical score and might therefore be beneficial in the rehabilitation assessments.